diff --git a/Cargo.lock b/Cargo.lock
index a2296dc10..35be07837 100644
--- a/Cargo.lock
+++ b/Cargo.lock
@@ -203,6 +203,17 @@ dependencies = [
  "tokio",
 ]
 
+[[package]]
+name = "async-recursion"
+version = "1.0.5"
+source = "registry+https://github.com/rust-lang/crates.io-index"
+checksum = "5fd55a5ba1179988837d24ab4c7cc8ed6efdeff578ede0416b4225a5fca35bd0"
+dependencies = [
+ "proc-macro2",
+ "quote",
+ "syn 2.0.48",
+]
+
 [[package]]
 name = "async-trait"
 version = "0.1.77"
@@ -2785,6 +2796,7 @@ version = "0.0.1"
 dependencies = [
  "anyhow",
  "assert_fs",
+ "async-recursion",
  "fs-err",
  "indoc",
  "insta",
@@ -2793,14 +2805,19 @@ dependencies = [
  "pep440_rs",
  "pep508_rs",
  "regex",
+ "reqwest",
+ "reqwest-middleware",
  "serde",
  "serde_json",
  "tempfile",
  "test-case",
  "thiserror",
+ "tokio",
  "tracing",
  "unscanny",
  "url",
+ "uv-cache",
+ "uv-client",
  "uv-fs",
  "uv-normalize",
  "uv-warnings",
diff --git a/Cargo.toml b/Cargo.toml
index 1d27788e7..e5fbf49de 100644
--- a/Cargo.toml
+++ b/Cargo.toml
@@ -3,7 +3,7 @@ members = ["crates/*"]
 exclude = [
   "scripts",
   # Needs nightly
-  "crates/uv-trampoline"
+  "crates/uv-trampoline",
 ]
 resolver = "2"
 
@@ -22,6 +22,7 @@ anyhow = { version = "1.0.80" }
 async-compression = { version = "0.4.6" }
 async-channel = { version = "2.2.0" }
 async-trait = { version = "0.1.77" }
+async-recursion = { version = "1.0.5" }
 async_http_range_reader = { version = "0.7.0" }
 async_zip = { git = "https://github.com/charliermarsh/rs-async-zip", rev = "d76801da0943de985254fc6255c0e476b57c5836", features = ["deflate"] }
 base64 = { version = "0.21.7" }
diff --git a/crates/requirements-txt/Cargo.toml b/crates/requirements-txt/Cargo.toml
index 0a3f24c2a..6ee3d3098 100644
--- a/crates/requirements-txt/Cargo.toml
+++ b/crates/requirements-txt/Cargo.toml
@@ -15,15 +15,21 @@ workspace = true
 [dependencies]
 pep440_rs = { path = "../pep440-rs", features = ["rkyv", "serde"] }
 pep508_rs = { path = "../pep508-rs", features = ["rkyv", "serde", "non-pep508-extensions"] }
+uv-cache = { path = "../uv-cache" }
+uv-client = { path = "../uv-client" }
 uv-fs = { path = "../uv-fs" }
 uv-normalize = { path = "../uv-normalize" }
 uv-warnings = { path = "../uv-warnings" }
 
+async-recursion = { workspace = true }
 fs-err = { workspace = true }
 once_cell = { workspace = true }
 regex = { workspace = true }
+reqwest = { workspace = true }
+reqwest-middleware = { workspace = true }
 serde = { workspace = true }
 thiserror = { workspace = true }
+tokio = { workspace = true }
 tracing = { workspace = true }
 unscanny = { workspace = true }
 url = { workspace = true }
diff --git a/crates/requirements-txt/src/lib.rs b/crates/requirements-txt/src/lib.rs
index bd4cf7efe..c14911c01 100644
--- a/crates/requirements-txt/src/lib.rs
+++ b/crates/requirements-txt/src/lib.rs
@@ -40,11 +40,13 @@ use std::io;
 use std::path::{Path, PathBuf};
 
 use serde::{Deserialize, Serialize};
-use tracing::{instrument, warn};
+use tracing::instrument;
 use unscanny::{Pattern, Scanner};
 use url::Url;
+use uv_client::RegistryClient;
 use uv_warnings::warn_user;
 
+use async_recursion::async_recursion;
 use pep508_rs::{
     expand_path_vars, split_scheme, Extras, Pep508Error, Pep508ErrorSource, Requirement, Scheme,
     VerbatimUrl,
@@ -321,28 +323,38 @@ pub struct RequirementsTxt {
 impl RequirementsTxt {
     /// See module level documentation
     #[instrument(skip_all, fields(requirements_txt = requirements_txt.as_ref().as_os_str().to_str()))]
-    pub fn parse(
+    pub async fn parse(
         requirements_txt: impl AsRef<Path>,
         working_dir: impl AsRef<Path>,
+        client: &RegistryClient,
     ) -> Result<Self, RequirementsTxtFileError> {
+        let requirements_txt = requirements_txt.as_ref();
+        let working_dir = working_dir.as_ref();
+
         let content =
-            uv_fs::read_to_string(&requirements_txt).map_err(|err| RequirementsTxtFileError {
-                file: requirements_txt.as_ref().to_path_buf(),
-                error: RequirementsTxtParserError::IO(err),
+            if requirements_txt.starts_with("http://") | requirements_txt.starts_with("https://") {
+                read_url_to_string(&requirements_txt, client).await
+            } else {
+                uv_fs::read_to_string(&requirements_txt)
+                    .await
+                    .map_err(RequirementsTxtParserError::IO)
+            }
+            .map_err(|err| RequirementsTxtFileError {
+                file: requirements_txt.to_path_buf(),
+                error: err,
             })?;
 
-        let working_dir = working_dir.as_ref();
-        let requirements_dir = requirements_txt.as_ref().parent().unwrap_or(working_dir);
-        let data = Self::parse_inner(&content, working_dir, requirements_dir).map_err(|err| {
-            RequirementsTxtFileError {
-                file: requirements_txt.as_ref().to_path_buf(),
+        let requirements_dir = requirements_txt.parent().unwrap_or(working_dir);
+        let data = Self::parse_inner(&content, working_dir, requirements_dir, client)
+            .await
+            .map_err(|err| RequirementsTxtFileError {
+                file: requirements_txt.to_path_buf(),
                 error: err,
-            }
-        })?;
+            })?;
         if data == Self::default() {
             warn_user!(
                 "Requirements file {} does not contain any dependencies",
-                requirements_txt.as_ref().display()
+                requirements_txt.simplified_display()
             );
         }
 
@@ -355,10 +367,12 @@ impl RequirementsTxt {
     /// the current working directory. However, relative paths to sub-files (e.g., `-r ../requirements.txt`)
     /// are resolved against the directory of the containing `requirements.txt` file, to match
     /// `pip`'s behavior.
-    pub fn parse_inner(
+    #[async_recursion]
+    pub async fn parse_inner(
         content: &str,
         working_dir: &Path,
         requirements_dir: &Path,
+        client: &RegistryClient,
     ) -> Result<Self, RequirementsTxtParserError> {
         let mut s = Scanner::new(content);
 
@@ -370,14 +384,20 @@ impl RequirementsTxt {
                     start,
                     end,
                 } => {
-                    let sub_file = requirements_dir.join(expand_path_vars(&filename).as_ref());
-                    let sub_requirements = Self::parse(&sub_file, working_dir).map_err(|err| {
-                        RequirementsTxtParserError::Subfile {
+                    let filename = expand_path_vars(&filename);
+                    let sub_file =
+                        if filename.starts_with("http://") || filename.starts_with("https://") {
+                            PathBuf::from(filename.as_ref())
+                        } else {
+                            requirements_dir.join(filename.as_ref())
+                        };
+                    let sub_requirements = Self::parse(&sub_file, working_dir, client)
+                        .await
+                        .map_err(|err| RequirementsTxtParserError::Subfile {
                             source: Box::new(err),
                             start,
                             end,
-                        }
-                    })?;
+                        })?;
 
                     // Disallow conflicting `--index-url` in nested `requirements` files.
                     if sub_requirements.index_url.is_some()
@@ -402,14 +422,20 @@ impl RequirementsTxt {
                     start,
                     end,
                 } => {
-                    let sub_file = requirements_dir.join(expand_path_vars(&filename).as_ref());
-                    let sub_constraints = Self::parse(&sub_file, working_dir).map_err(|err| {
-                        RequirementsTxtParserError::Subfile {
+                    let filename = expand_path_vars(&filename);
+                    let sub_file =
+                        if filename.starts_with("http://") || filename.starts_with("https://") {
+                            PathBuf::from(filename.as_ref())
+                        } else {
+                            requirements_dir.join(filename.as_ref())
+                        };
+                    let sub_constraints = Self::parse(&sub_file, working_dir, client)
+                        .await
+                        .map_err(|err| RequirementsTxtParserError::Subfile {
                             source: Box::new(err),
                             start,
                             end,
-                        }
-                    })?;
+                        })?;
                     // Treat any nested requirements or constraints as constraints. This differs
                     // from `pip`, which seems to treat `-r` requirements in constraints files as
                     // _requirements_, but we don't want to support that.
@@ -767,6 +793,31 @@ fn parse_value<'a, T>(
     }
 }
 
+/// Fetch the contents of a URL and return them as a string.
+async fn read_url_to_string(
+    path: impl AsRef<Path>,
+    client: &RegistryClient,
+) -> Result<String, RequirementsTxtParserError> {
+    // pip would URL-encode the non-UTF-8 bytes of the string; we just don't support them.
+    let path_utf8 =
+        path.as_ref()
+            .to_str()
+            .ok_or_else(|| RequirementsTxtParserError::NonUnicodeUrl {
+                url: path.as_ref().to_owned(),
+            })?;
+    Ok(client
+        .cached_client()
+        .uncached()
+        .get(path_utf8)
+        .send()
+        .await?
+        .error_for_status()
+        .map_err(reqwest_middleware::Error::Reqwest)?
+        .text()
+        .await
+        .map_err(reqwest_middleware::Error::Reqwest)?)
+}
+
 /// Error parsing requirements.txt, wrapper with filename
 #[derive(Debug)]
 pub struct RequirementsTxtFileError {
@@ -808,6 +859,10 @@ pub enum RequirementsTxtParserError {
         start: usize,
         end: usize,
     },
+    Reqwest(reqwest_middleware::Error),
+    NonUnicodeUrl {
+        url: PathBuf,
+    },
 }
 
 impl RequirementsTxtParserError {
@@ -855,6 +910,8 @@ impl RequirementsTxtParserError {
                 start: start + offset,
                 end: end + offset,
             },
+            Self::Reqwest(err) => Self::Reqwest(err),
+            Self::NonUnicodeUrl { url } => Self::NonUnicodeUrl { url },
         }
     }
 }
@@ -897,6 +954,16 @@ impl Display for RequirementsTxtParserError {
             Self::Subfile { start, .. } => {
                 write!(f, "Error parsing included file at position {start}")
             }
+            Self::Reqwest(err) => {
+                write!(f, "Error while accessing remote requirements file {err}")
+            }
+            Self::NonUnicodeUrl { url } => {
+                write!(
+                    f,
+                    "Remote requirements URL contains non-unicode characters: {}",
+                    url.display(),
+                )
+            }
         }
     }
 }
@@ -914,6 +981,8 @@ impl std::error::Error for RequirementsTxtParserError {
             Self::Pep508 { source, .. } => Some(source),
             Self::Subfile { source, .. } => Some(source.as_ref()),
             Self::Parser { .. } => None,
+            Self::Reqwest(err) => err.source(),
+            Self::NonUnicodeUrl { .. } => None,
         }
     }
 }
@@ -989,6 +1058,21 @@ impl Display for RequirementsTxtFileError {
                     self.file.simplified_display(),
                 )
             }
+            RequirementsTxtParserError::Reqwest(err) => {
+                write!(
+                    f,
+                    "Error while accessing remote requirements file {}: {err}",
+                    self.file.simplified_display(),
+                )
+            }
+
+            RequirementsTxtParserError::NonUnicodeUrl { url } => {
+                write!(
+                    f,
+                    "Remote requirements URL contains non-unicode characters: {}",
+                    url.display(),
+                )
+            }
         }
     }
 }
@@ -1005,6 +1089,12 @@ impl From<io::Error> for RequirementsTxtParserError {
     }
 }
 
+impl From<reqwest_middleware::Error> for RequirementsTxtParserError {
+    fn from(err: reqwest_middleware::Error) -> Self {
+        Self::Reqwest(err)
+    }
+}
+
 /// Calculates the column and line offset of a given cursor based on the
 /// number of Unicode codepoints.
 fn calculate_row_column(content: &str, position: usize) -> (usize, usize) {
@@ -1057,6 +1147,7 @@ mod test {
     use tempfile::tempdir;
     use test_case::test_case;
     use unscanny::Scanner;
+    use uv_client::{RegistryClient, RegistryClientBuilder};
     use uv_fs::Simplified;
 
     use crate::{calculate_row_column, EditableRequirement, RequirementsTxt};
@@ -1065,6 +1156,12 @@ mod test {
         PathBuf::from("./test-data")
     }
 
+    fn registry_client() -> RegistryClient {
+        RegistryClientBuilder::new(uv_cache::Cache::temp().unwrap())
+            .connectivity(uv_client::Connectivity::Online)
+            .build()
+    }
+
     #[test_case(Path::new("basic.txt"))]
     #[test_case(Path::new("constraints-a.txt"))]
     #[test_case(Path::new("constraints-b.txt"))]
@@ -1075,11 +1172,14 @@ mod test {
     #[test_case(Path::new("poetry-with-hashes.txt"))]
     #[test_case(Path::new("small.txt"))]
     #[test_case(Path::new("whitespace.txt"))]
-    fn parse(path: &Path) {
+    #[tokio::test]
+    async fn parse(path: &Path) {
         let working_dir = workspace_test_data_dir().join("requirements-txt");
         let requirements_txt = working_dir.join(path);
 
-        let actual = RequirementsTxt::parse(requirements_txt, &working_dir).unwrap();
+        let actual = RequirementsTxt::parse(requirements_txt, &working_dir, &registry_client())
+            .await
+            .unwrap();
 
         let snapshot = format!("parse-{}", path.to_string_lossy());
         insta::assert_debug_snapshot!(snapshot, actual);
@@ -1096,7 +1196,8 @@ mod test {
     #[test_case(Path::new("small.txt"))]
     #[test_case(Path::new("whitespace.txt"))]
     #[test_case(Path::new("editable.txt"))]
-    fn line_endings(path: &Path) {
+    #[tokio::test]
+    async fn line_endings(path: &Path) {
         let working_dir = workspace_test_data_dir().join("requirements-txt");
         let requirements_txt = working_dir.join(path);
 
@@ -1120,14 +1221,16 @@ mod test {
         let requirements_txt = temp_dir.path().join(path);
         fs::write(&requirements_txt, contents).unwrap();
 
-        let actual = RequirementsTxt::parse(&requirements_txt, &working_dir).unwrap();
+        let actual = RequirementsTxt::parse(&requirements_txt, &working_dir, &registry_client())
+            .await
+            .unwrap();
 
         let snapshot = format!("line-endings-{}", path.to_string_lossy());
         insta::assert_debug_snapshot!(snapshot, actual);
     }
 
-    #[test]
-    fn invalid_include_missing_file() -> Result<()> {
+    #[tokio::test]
+    async fn invalid_include_missing_file() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
         let missing_txt = temp_dir.child("missing.txt");
         let requirements_txt = temp_dir.child("requirements.txt");
@@ -1135,7 +1238,10 @@ mod test {
             -r missing.txt
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error)
             .chain()
             // The last error is operating-system specific.
@@ -1155,22 +1261,25 @@ mod test {
         }, {
             insta::assert_snapshot!(errors, @r###"
             Error parsing included file in `<REQUIREMENTS_TXT>` at position 0
-            failed to open file `<MISSING_TXT>`
+            failed to read from file `<MISSING_TXT>`
             "###);
         });
 
         Ok(())
     }
 
-    #[test]
-    fn invalid_requirement() -> Result<()> {
+    #[tokio::test]
+    async fn invalid_requirement() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
         let requirements_txt = temp_dir.child("requirements.txt");
         requirements_txt.write_str(indoc! {"
             numpy[ö]==1.29
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
@@ -1193,15 +1302,18 @@ mod test {
         Ok(())
     }
 
-    #[test]
-    fn unsupported_editable() -> Result<()> {
+    #[tokio::test]
+    async fn unsupported_editable() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
         let requirements_txt = temp_dir.child("requirements.txt");
         requirements_txt.write_str(indoc! {"
             -e http://localhost:8080/
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
@@ -1219,15 +1331,18 @@ mod test {
         Ok(())
     }
 
-    #[test]
-    fn invalid_editable_extra() -> Result<()> {
+    #[tokio::test]
+    async fn invalid_editable_extra() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
         let requirements_txt = temp_dir.child("requirements.txt");
         requirements_txt.write_str(indoc! {"
             -e black[,abcdef]
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
@@ -1247,15 +1362,18 @@ mod test {
         Ok(())
     }
 
-    #[test]
-    fn invalid_index_url() -> Result<()> {
+    #[tokio::test]
+    async fn invalid_index_url() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
         let requirements_txt = temp_dir.child("requirements.txt");
         requirements_txt.write_str(indoc! {"
             --index-url 123
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
@@ -1276,8 +1394,8 @@ mod test {
         Ok(())
     }
 
-    #[test]
-    fn missing_r() -> Result<()> {
+    #[tokio::test]
+    async fn missing_r() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
 
         let file_txt = temp_dir.child("file.txt");
@@ -1289,7 +1407,10 @@ mod test {
             file.txt
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
@@ -1307,8 +1428,8 @@ mod test {
         Ok(())
     }
 
-    #[test]
-    fn relative_requirement() -> Result<()> {
+    #[tokio::test]
+    async fn relative_requirement() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
 
         // Create a requirements file with a relative entry, in a subdirectory.
@@ -1330,7 +1451,10 @@ mod test {
             -r subdir/child.txt
         "})?;
 
-        let requirements = RequirementsTxt::parse(parent_txt.path(), temp_dir.path()).unwrap();
+        let requirements =
+            RequirementsTxt::parse(parent_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap();
         insta::assert_debug_snapshot!(requirements, @r###"
         RequirementsTxt {
             requirements: [
@@ -1359,9 +1483,9 @@ mod test {
         Ok(())
     }
 
-    #[test]
+    #[tokio::test]
     #[cfg(not(windows))]
-    fn nested_editable() -> Result<()> {
+    async fn nested_editable() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
 
         let requirements_txt = temp_dir.child("requirements.txt");
@@ -1381,7 +1505,9 @@ mod test {
         "})?;
 
         let requirements =
-            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap();
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap();
 
         insta::assert_debug_snapshot!(requirements, @r###"
             RequirementsTxt {
@@ -1419,8 +1545,8 @@ mod test {
         Ok(())
     }
 
-    #[test]
-    fn nested_conflicting_index_url() -> Result<()> {
+    #[tokio::test]
+    async fn nested_conflicting_index_url() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
 
         let requirements_txt = temp_dir.child("requirements.txt");
@@ -1439,7 +1565,10 @@ mod test {
             --index-url https://fake.pypi.org/simple
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
@@ -1477,8 +1606,8 @@ mod test {
         );
     }
 
-    #[test]
-    fn parser_error_line_and_column() -> Result<()> {
+    #[tokio::test]
+    async fn parser_error_line_and_column() -> Result<()> {
         let temp_dir = assert_fs::TempDir::new()?;
         let requirements_txt = temp_dir.child("requirements.txt");
         requirements_txt.write_str(indoc! {"
@@ -1487,7 +1616,10 @@ mod test {
             tqdm
         "})?;
 
-        let error = RequirementsTxt::parse(requirements_txt.path(), temp_dir.path()).unwrap_err();
+        let error =
+            RequirementsTxt::parse(requirements_txt.path(), temp_dir.path(), &registry_client())
+                .await
+                .unwrap_err();
         let errors = anyhow::Error::new(error).chain().join("\n");
 
         let requirement_txt =
diff --git a/crates/uv-client/src/registry_client.rs b/crates/uv-client/src/registry_client.rs
index 7ae8c95b0..5adc72e51 100644
--- a/crates/uv-client/src/registry_client.rs
+++ b/crates/uv-client/src/registry_client.rs
@@ -177,6 +177,12 @@ impl RegistryClient {
         self.timeout
     }
 
+    /// Set the index URLs to use for fetching packages.
+    #[must_use]
+    pub fn with_index_url(self, index_urls: IndexUrls) -> Self {
+        Self { index_urls, ..self }
+    }
+
     /// Fetch a package from the `PyPI` simple API.
     ///
     /// "simple" here refers to [PEP 503 – Simple Repository API](https://peps.python.org/pep-0503/)
diff --git a/crates/uv-fs/src/lib.rs b/crates/uv-fs/src/lib.rs
index 11db64995..3598c419b 100644
--- a/crates/uv-fs/src/lib.rs
+++ b/crates/uv-fs/src/lib.rs
@@ -1,4 +1,5 @@
 use std::fmt::Display;
+use std::io::Read;
 use std::path::{Path, PathBuf};
 
 use fs2::FileExt;
@@ -12,35 +13,31 @@ pub use crate::path::*;
 
 mod path;
 
-/// Reads the contents of the file path given into memory.
+/// Reads the contents of the file path into memory.
 ///
 /// If the file path is `-`, then contents are read from stdin instead.
-pub fn read(path: impl AsRef<Path>) -> std::io::Result<Vec<u8>> {
-    use std::io::Read;
-
+pub async fn read(path: impl AsRef<Path>) -> std::io::Result<Vec<u8>> {
     let path = path.as_ref();
     if path == Path::new("-") {
         let mut buf = Vec::with_capacity(1024);
         std::io::stdin().read_to_end(&mut buf)?;
         Ok(buf)
     } else {
-        fs::read(path)
+        fs_err::tokio::read(path).await
     }
 }
 
-/// Reads the contents of the file path given into memory as a `String`.
+/// Reads the contents of the file path into memory as a `String`.
 ///
 /// If the file path is `-`, then contents are read from stdin instead.
-pub fn read_to_string(path: impl AsRef<Path>) -> std::io::Result<String> {
-    use std::io::Read;
-
+pub async fn read_to_string(path: impl AsRef<Path>) -> std::io::Result<String> {
     let path = path.as_ref();
     if path == Path::new("-") {
         let mut buf = String::with_capacity(1024);
         std::io::stdin().read_to_string(&mut buf)?;
         Ok(buf)
     } else {
-        fs::read_to_string(path)
+        fs_err::tokio::read_to_string(path).await
     }
 }
 
diff --git a/crates/uv/src/commands/pip_compile.rs b/crates/uv/src/commands/pip_compile.rs
index 5ba3b6db6..68a1e1ed1 100644
--- a/crates/uv/src/commands/pip_compile.rs
+++ b/crates/uv/src/commands/pip_compile.rs
@@ -9,6 +9,7 @@ use std::str::FromStr;
 use anstream::{eprint, AutoStream, StripStream};
 use anyhow::{anyhow, Context, Result};
 use chrono::{DateTime, Utc};
+use futures::future::OptionFuture;
 use itertools::Itertools;
 use owo_colors::OwoColorize;
 use rustc_hash::FxHashSet;
@@ -82,6 +83,11 @@ pub(crate) async fn pip_compile(
         ));
     }
 
+    // Initialize the registry client.
+    let client = RegistryClientBuilder::new(cache.clone())
+        .connectivity(connectivity)
+        .build();
+
     // Read all requirements from the provided sources.
     let RequirementsSpecification {
         project,
@@ -94,11 +100,14 @@ pub(crate) async fn pip_compile(
         no_index,
         find_links,
         extras: used_extras,
-    } = RequirementsSpecification::from_sources(requirements, constraints, overrides, &extras)?;
-
-    // Incorporate any index locations from the provided sources.
-    let index_locations =
-        index_locations.combine(index_url, extra_index_urls, find_links, no_index);
+    } = RequirementsSpecification::from_sources(
+        requirements,
+        constraints,
+        overrides,
+        &extras,
+        &client,
+    )
+    .await?;
 
     // Check that all provided extras are used
     if let ExtrasSpecification::Some(extras) = extras {
@@ -117,28 +126,33 @@ pub(crate) async fn pip_compile(
         }
     }
 
-    let preferences: Vec<Requirement> = output_file
-        // As an optimization, skip reading the lockfile is we're upgrading all packages anyway.
-        .filter(|_| !upgrade.is_all())
-        .filter(|output_file| output_file.exists())
-        .map(Path::to_path_buf)
-        .map(RequirementsSource::from_path)
-        .as_ref()
-        .map(|source| RequirementsSpecification::from_source(source, &extras))
-        .transpose()?
-        .map(|spec| spec.requirements)
-        .map(|requirements| match upgrade {
-            // Respect all pinned versions from the existing lockfile.
-            Upgrade::None => requirements,
-            // Ignore all pinned versions from the existing lockfile.
-            Upgrade::All => vec![],
-            // Ignore pinned versions for the specified packages.
-            Upgrade::Packages(packages) => requirements
-                .into_iter()
-                .filter(|requirement| !packages.contains(&requirement.name))
-                .collect(),
-        })
-        .unwrap_or_default();
+    let preferences: Vec<Requirement> = OptionFuture::from(
+        output_file
+            // As an optimization, skip reading the lockfile is we're upgrading all packages anyway.
+            .filter(|_| !upgrade.is_all())
+            .filter(|output_file| output_file.exists())
+            .map(Path::to_path_buf)
+            .map(RequirementsSource::from_path)
+            .as_ref()
+            .map(|source| async {
+                RequirementsSpecification::from_source(source, &extras, &client).await
+            }),
+    )
+    .await
+    .transpose()?
+    .map(|spec| spec.requirements)
+    .map(|requirements| match upgrade {
+        // Respect all pinned versions from the existing lockfile.
+        Upgrade::None => requirements,
+        // Ignore all pinned versions from the existing lockfile.
+        Upgrade::All => vec![],
+        // Ignore pinned versions for the specified packages.
+        Upgrade::Packages(packages) => requirements
+            .into_iter()
+            .filter(|requirement| !packages.contains(&requirement.name))
+            .collect(),
+    })
+    .unwrap_or_default();
 
     // Find an interpreter to use for building distributions
     let platform = Platform::current()?;
@@ -196,11 +210,13 @@ pub(crate) async fn pip_compile(
         |python_version| Cow::Owned(python_version.markers(interpreter.markers())),
     );
 
-    // Instantiate a client.
-    let client = RegistryClientBuilder::new(cache.clone())
-        .index_urls(index_locations.index_urls())
-        .connectivity(connectivity)
-        .build();
+    // Incorporate any index locations from the provided sources.
+    let index_locations =
+        index_locations.combine(index_url, extra_index_urls, find_links, no_index);
+
+    // Update the index URLs on the client, to take into account any index URLs added by the
+    // sources (e.g., `--index-url` in a `requirements.txt` file).
+    let client = client.with_index_url(index_locations.index_urls());
 
     // Resolve the flat indexes from `--find-links`.
     let flat_index = {
diff --git a/crates/uv/src/commands/pip_install.rs b/crates/uv/src/commands/pip_install.rs
index 53b2c57ee..ec44703d0 100644
--- a/crates/uv/src/commands/pip_install.rs
+++ b/crates/uv/src/commands/pip_install.rs
@@ -70,6 +70,11 @@ pub(crate) async fn pip_install(
 ) -> Result<ExitStatus> {
     let start = std::time::Instant::now();
 
+    // Initialize the registry client.
+    let client = RegistryClientBuilder::new(cache.clone())
+        .connectivity(connectivity)
+        .build();
+
     // Read all requirements from the provided sources.
     let RequirementsSpecification {
         project,
@@ -82,11 +87,7 @@ pub(crate) async fn pip_install(
         no_index,
         find_links,
         extras: used_extras,
-    } = specification(requirements, constraints, overrides, extras)?;
-
-    // Incorporate any index locations from the provided sources.
-    let index_locations =
-        index_locations.combine(index_url, extra_index_urls, find_links, no_index);
+    } = specification(requirements, constraints, overrides, extras, &client).await?;
 
     // Check that all provided extras are used
     if let ExtrasSpecification::Some(extras) = extras {
@@ -169,11 +170,13 @@ pub(crate) async fn pip_install(
     let tags = venv.interpreter().tags()?;
     let markers = venv.interpreter().markers();
 
-    // Instantiate a client.
-    let client = RegistryClientBuilder::new(cache.clone())
-        .index_urls(index_locations.index_urls())
-        .connectivity(connectivity)
-        .build();
+    // Incorporate any index locations from the provided sources.
+    let index_locations =
+        index_locations.combine(index_url, extra_index_urls, find_links, no_index);
+
+    // Update the index URLs on the client, to take into account any index URLs added by the
+    // sources (e.g., `--index-url` in a `requirements.txt` file).
+    let client = client.with_index_url(index_locations.index_urls());
 
     // Resolve the flat indexes from `--find-links`.
     let flat_index = {
@@ -316,11 +319,12 @@ pub(crate) async fn pip_install(
 }
 
 /// Consolidate the requirements for an installation.
-fn specification(
+async fn specification(
     requirements: &[RequirementsSource],
     constraints: &[RequirementsSource],
     overrides: &[RequirementsSource],
     extras: &ExtrasSpecification<'_>,
+    client: &RegistryClient,
 ) -> Result<RequirementsSpecification, Error> {
     // If the user requests `extras` but does not provide a pyproject toml source
     if !matches!(extras, ExtrasSpecification::None)
@@ -332,8 +336,14 @@ fn specification(
     }
 
     // Read all requirements from the provided sources.
-    let spec =
-        RequirementsSpecification::from_sources(requirements, constraints, overrides, extras)?;
+    let spec = RequirementsSpecification::from_sources(
+        requirements,
+        constraints,
+        overrides,
+        extras,
+        client,
+    )
+    .await?;
 
     // Check that all provided extras are used
     if let ExtrasSpecification::Some(extras) = extras {
diff --git a/crates/uv/src/commands/pip_sync.rs b/crates/uv/src/commands/pip_sync.rs
index 565869328..a61551537 100644
--- a/crates/uv/src/commands/pip_sync.rs
+++ b/crates/uv/src/commands/pip_sync.rs
@@ -48,6 +48,11 @@ pub(crate) async fn pip_sync(
 ) -> Result<ExitStatus> {
     let start = std::time::Instant::now();
 
+    // Initialize the registry client.
+    let client = RegistryClientBuilder::new(cache.clone())
+        .connectivity(connectivity)
+        .build();
+
     // Read all requirements from the provided sources.
     let RequirementsSpecification {
         project: _project,
@@ -60,7 +65,7 @@ pub(crate) async fn pip_sync(
         no_index,
         find_links,
         extras: _extras,
-    } = RequirementsSpecification::from_simple_sources(sources)?;
+    } = RequirementsSpecification::from_simple_sources(sources, &client).await?;
 
     let num_requirements = requirements.len() + editables.len();
     if num_requirements == 0 {
@@ -68,10 +73,6 @@ pub(crate) async fn pip_sync(
         return Ok(ExitStatus::Success);
     }
 
-    // Incorporate any index locations from the provided sources.
-    let index_locations =
-        index_locations.combine(index_url, extra_index_urls, find_links, no_index);
-
     // Detect the current Python interpreter.
     let platform = Platform::current()?;
     let venv = if let Some(python) = python.as_ref() {
@@ -108,11 +109,13 @@ pub(crate) async fn pip_sync(
     // Determine the current environment markers.
     let tags = venv.interpreter().tags()?;
 
-    // Prep the registry client.
-    let client = RegistryClientBuilder::new(cache.clone())
-        .index_urls(index_locations.index_urls())
-        .connectivity(connectivity)
-        .build();
+    // Incorporate any index locations from the provided sources.
+    let index_locations =
+        index_locations.combine(index_url, extra_index_urls, find_links, no_index);
+
+    // Update the index URLs on the client, to take into account any index URLs added by the
+    // sources (e.g., `--index-url` in a `requirements.txt` file).
+    let client = client.with_index_url(index_locations.index_urls());
 
     // Resolve the flat indexes from `--find-links`.
     let flat_index = {
diff --git a/crates/uv/src/commands/pip_uninstall.rs b/crates/uv/src/commands/pip_uninstall.rs
index 63715c06e..007915b56 100644
--- a/crates/uv/src/commands/pip_uninstall.rs
+++ b/crates/uv/src/commands/pip_uninstall.rs
@@ -7,6 +7,7 @@ use tracing::debug;
 use distribution_types::{InstalledMetadata, Name};
 use platform_host::Platform;
 use uv_cache::Cache;
+use uv_client::{Connectivity, RegistryClientBuilder};
 use uv_fs::Simplified;
 use uv_interpreter::PythonEnvironment;
 
@@ -20,10 +21,16 @@ pub(crate) async fn pip_uninstall(
     python: Option<String>,
     system: bool,
     cache: Cache,
+    connectivity: Connectivity,
     printer: Printer,
 ) -> Result<ExitStatus> {
     let start = std::time::Instant::now();
 
+    // Initialize the registry client.
+    let client: uv_client::RegistryClient = RegistryClientBuilder::new(cache.clone())
+        .connectivity(connectivity)
+        .build();
+
     // Read all requirements from the provided sources.
     let RequirementsSpecification {
         project: _project,
@@ -36,7 +43,7 @@ pub(crate) async fn pip_uninstall(
         no_index: _no_index,
         find_links: _find_links,
         extras: _extras,
-    } = RequirementsSpecification::from_simple_sources(sources)?;
+    } = RequirementsSpecification::from_simple_sources(sources, &client).await?;
 
     // Detect the current Python interpreter.
     let platform = Platform::current()?;
diff --git a/crates/uv/src/main.rs b/crates/uv/src/main.rs
index 92e0c1084..d0330d137 100644
--- a/crates/uv/src/main.rs
+++ b/crates/uv/src/main.rs
@@ -861,6 +861,10 @@ struct PipUninstallArgs {
     /// should be used with caution, as it can modify the system Python installation.
     #[clap(long, conflicts_with = "python")]
     system: bool,
+
+    /// Run offline, i.e., without accessing the network.
+    #[arg(global = true, long)]
+    offline: bool,
 }
 
 #[derive(Args)]
@@ -1455,7 +1459,19 @@ async fn run() -> Result<ExitStatus> {
                         .map(RequirementsSource::from_path),
                 )
                 .collect::<Vec<_>>();
-            commands::pip_uninstall(&sources, args.python, args.system, cache, printer).await
+            commands::pip_uninstall(
+                &sources,
+                args.python,
+                args.system,
+                cache,
+                if args.offline {
+                    Connectivity::Offline
+                } else {
+                    Connectivity::Online
+                },
+                printer,
+            )
+            .await
         }
         Commands::Pip(PipNamespace {
             command: PipCommand::Freeze(args),
diff --git a/crates/uv/src/requirements.rs b/crates/uv/src/requirements.rs
index f7d9fb0c9..31db38181 100644
--- a/crates/uv/src/requirements.rs
+++ b/crates/uv/src/requirements.rs
@@ -12,6 +12,7 @@ use distribution_types::{FlatIndexLocation, IndexUrl};
 use pep508_rs::Requirement;
 use requirements_txt::{EditableRequirement, FindLink, RequirementsTxt};
 use tracing::{instrument, Level};
+use uv_client::RegistryClient;
 use uv_fs::Simplified;
 use uv_normalize::{ExtraName, PackageName};
 
@@ -138,9 +139,10 @@ pub(crate) struct RequirementsSpecification {
 impl RequirementsSpecification {
     /// Read the requirements and constraints from a source.
     #[instrument(skip_all, level = Level::DEBUG, fields(source = % source))]
-    pub(crate) fn from_source(
+    pub(crate) async fn from_source(
         source: &RequirementsSource,
-        extras: &ExtrasSpecification,
+        extras: &ExtrasSpecification<'_>,
+        client: &RegistryClient,
     ) -> Result<Self> {
         Ok(match source {
             RequirementsSource::Package(name) => {
@@ -176,7 +178,8 @@ impl RequirementsSpecification {
                 }
             }
             RequirementsSource::RequirementsTxt(path) => {
-                let requirements_txt = RequirementsTxt::parse(path, std::env::current_dir()?)?;
+                let requirements_txt =
+                    RequirementsTxt::parse(path, std::env::current_dir()?, client).await?;
                 Self {
                     project: None,
                     requirements: requirements_txt
@@ -206,7 +209,7 @@ impl RequirementsSpecification {
                 }
             }
             RequirementsSource::PyprojectToml(path) => {
-                let contents = uv_fs::read_to_string(path)?;
+                let contents = uv_fs::read_to_string(path).await?;
                 let pyproject_toml = toml::from_str::<pyproject_toml::PyProjectToml>(&contents)
                     .with_context(|| format!("Failed to parse `{}`", path.simplified_display()))?;
                 let mut used_extras = FxHashSet::default();
@@ -273,11 +276,12 @@ impl RequirementsSpecification {
     }
 
     /// Read the combined requirements and constraints from a set of sources.
-    pub(crate) fn from_sources(
+    pub(crate) async fn from_sources(
         requirements: &[RequirementsSource],
         constraints: &[RequirementsSource],
         overrides: &[RequirementsSource],
-        extras: &ExtrasSpecification,
+        extras: &ExtrasSpecification<'_>,
+        client: &RegistryClient,
     ) -> Result<Self> {
         let mut spec = Self::default();
 
@@ -285,7 +289,7 @@ impl RequirementsSpecification {
         // A `requirements.txt` can contain a `-c constraints.txt` directive within it, so reading
         // a requirements file can also add constraints.
         for source in requirements {
-            let source = Self::from_source(source, extras)?;
+            let source = Self::from_source(source, extras, client).await?;
             spec.requirements.extend(source.requirements);
             spec.constraints.extend(source.constraints);
             spec.overrides.extend(source.overrides);
@@ -312,7 +316,7 @@ impl RequirementsSpecification {
 
         // Read all constraints, treating _everything_ as a constraint.
         for source in constraints {
-            let source = Self::from_source(source, extras)?;
+            let source = Self::from_source(source, extras, client).await?;
             spec.constraints.extend(source.requirements);
             spec.constraints.extend(source.constraints);
             spec.constraints.extend(source.overrides);
@@ -332,7 +336,7 @@ impl RequirementsSpecification {
 
         // Read all overrides, treating both requirements _and_ constraints as overrides.
         for source in overrides {
-            let source = Self::from_source(source, extras)?;
+            let source = Self::from_source(source, extras, client).await?;
             spec.overrides.extend(source.requirements);
             spec.overrides.extend(source.constraints);
             spec.overrides.extend(source.overrides);
@@ -354,8 +358,11 @@ impl RequirementsSpecification {
     }
 
     /// Read the requirements from a set of sources.
-    pub(crate) fn from_simple_sources(requirements: &[RequirementsSource]) -> Result<Self> {
-        Self::from_sources(requirements, &[], &[], &ExtrasSpecification::None)
+    pub(crate) async fn from_simple_sources(
+        requirements: &[RequirementsSource],
+        client: &RegistryClient,
+    ) -> Result<Self> {
+        Self::from_sources(requirements, &[], &[], &ExtrasSpecification::None, client).await
     }
 }
 
diff --git a/crates/uv/tests/pip_compile.rs b/crates/uv/tests/pip_compile.rs
index d3d295de4..1eddd1e77 100644
--- a/crates/uv/tests/pip_compile.rs
+++ b/crates/uv/tests/pip_compile.rs
@@ -115,7 +115,7 @@ fn missing_requirements_in() {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `requirements.in`
+    error: failed to read from file `requirements.in`
       Caused by: No such file or directory (os error 2)
     "###
     );
@@ -142,7 +142,7 @@ fn missing_venv() -> Result<()> {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `requirements.in`
+    error: failed to read from file `requirements.in`
       Caused by: No such file or directory (os error 2)
     "###
     );
diff --git a/crates/uv/tests/pip_install.rs b/crates/uv/tests/pip_install.rs
index 9bd24d3c1..527e7cda1 100644
--- a/crates/uv/tests/pip_install.rs
+++ b/crates/uv/tests/pip_install.rs
@@ -100,7 +100,7 @@ fn missing_requirements_txt() {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `requirements.txt`
+    error: failed to read from file `requirements.txt`
       Caused by: No such file or directory (os error 2)
     "###
     );
@@ -1509,6 +1509,73 @@ fn install_constraints_inline() -> Result<()> {
     Ok(())
 }
 
+/// Install a package from a `constraints.txt` file on a remote http server.
+#[test]
+fn install_constraints_remote() {
+    let context = TestContext::new("3.12");
+
+    uv_snapshot!(command(&context)
+            .arg("-c")
+            .arg("https://raw.githubusercontent.com/apache/airflow/constraints-2-6/constraints-3.11.txt")
+            .arg("typing_extensions>=4.0"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 1 package in [TIME]
+    Downloaded 1 package in [TIME]
+    Installed 1 package in [TIME]
+     + typing-extensions==4.7.1
+    "###
+    ); // would yield typing-extensions==4.8.2 without constraint file
+}
+
+/// Install a package from a `requirements.txt` file, with an inline constraint, which points
+/// to a remote http server.
+#[test]
+fn install_constraints_inline_remote() -> Result<()> {
+    let context = TestContext::new("3.12");
+    let requirementstxt = context.temp_dir.child("requirements.txt");
+    requirementstxt.write_str("typing-extensions>=4.0\n-c https://raw.githubusercontent.com/apache/airflow/constraints-2-6/constraints-3.11.txt")?;
+
+    uv_snapshot!(command(&context)
+            .arg("-r")
+            .arg("requirements.txt"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 1 package in [TIME]
+    Downloaded 1 package in [TIME]
+    Installed 1 package in [TIME]
+     + typing-extensions==4.7.1
+    "### // would yield typing-extensions==4.8.2 without constraint file
+    );
+
+    Ok(())
+}
+
+#[test]
+fn install_constraints_respects_offline_mode() {
+    let context = TestContext::new("3.12");
+
+    uv_snapshot!(command(&context)
+            .arg("--offline")
+            .arg("-r")
+            .arg("http://example.com/requirements.txt"), @r###"
+    success: false
+    exit_code: 2
+    ----- stdout -----
+
+    ----- stderr -----
+    error: Error while accessing remote requirements file http://example.com/requirements.txt: Middleware error: Network connectivity is disabled, but the requested data wasn't found in the cache for: `http://example.com/requirements.txt`
+      Caused by: Network connectivity is disabled, but the requested data wasn't found in the cache for: `http://example.com/requirements.txt`
+    "###
+    );
+}
+
 /// Tests that we can install `polars==0.14.0`, which has this odd dependency
 /// requirement in its wheel metadata: `pyarrow>=4.0.*; extra == 'pyarrow'`.
 ///
diff --git a/crates/uv/tests/pip_sync.rs b/crates/uv/tests/pip_sync.rs
index 338a98eb5..b10c6bf8a 100644
--- a/crates/uv/tests/pip_sync.rs
+++ b/crates/uv/tests/pip_sync.rs
@@ -124,7 +124,7 @@ fn missing_requirements_txt() {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `requirements.txt`
+    error: failed to read from file `requirements.txt`
       Caused by: No such file or directory (os error 2)
     "###);
 
@@ -151,7 +151,7 @@ fn missing_venv() -> Result<()> {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `requirements.txt`
+    error: failed to read from file `requirements.txt`
       Caused by: No such file or directory (os error 2)
     "###);
 
diff --git a/crates/uv/tests/pip_uninstall.rs b/crates/uv/tests/pip_uninstall.rs
index 18ee8d7cf..3bb9eda52 100644
--- a/crates/uv/tests/pip_uninstall.rs
+++ b/crates/uv/tests/pip_uninstall.rs
@@ -75,7 +75,7 @@ fn missing_requirements_txt() -> Result<()> {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `requirements.txt`
+    error: failed to read from file `requirements.txt`
       Caused by: No such file or directory (os error 2)
     "###
     );
@@ -125,7 +125,7 @@ fn missing_pyproject_toml() -> Result<()> {
     ----- stdout -----
 
     ----- stderr -----
-    error: failed to open file `pyproject.toml`
+    error: failed to read from file `pyproject.toml`
       Caused by: No such file or directory (os error 2)
     "###
     );