diff --git a/crates/uv-scripts/src/lib.rs b/crates/uv-scripts/src/lib.rs
index 46263eb1d..ca74c834a 100644
--- a/crates/uv-scripts/src/lib.rs
+++ b/crates/uv-scripts/src/lib.rs
@@ -14,7 +14,7 @@ static FINDER: LazyLock<Finder> = LazyLock::new(|| Finder::new(b"# /// script"))
 #[derive(Debug, Serialize, Deserialize)]
 #[serde(rename_all = "kebab-case")]
 pub struct Pep723Metadata {
-    pub dependencies: Vec<pep508_rs::Requirement<VerbatimParsedUrl>>,
+    pub dependencies: Option<Vec<pep508_rs::Requirement<VerbatimParsedUrl>>>,
     pub requires_python: Option<pep440_rs::VersionSpecifiers>,
 }
 
diff --git a/crates/uv/src/commands/project/run.rs b/crates/uv/src/commands/project/run.rs
index 6a41d9e53..0da9643e0 100644
--- a/crates/uv/src/commands/project/run.rs
+++ b/crates/uv/src/commands/project/run.rs
@@ -92,6 +92,7 @@ pub(crate) async fn run(
     let reporter = PythonDownloadReporter::single(printer.filter(show_resolution));
 
     // Determine whether the command to execute is a PEP 723 script.
+    let temp_dir;
     let script_interpreter = if let RunCommand::Python(target, _) = &command {
         if let Some(metadata) = uv_scripts::read_pep723_metadata(&target).await? {
             writeln!(
@@ -129,28 +130,39 @@ pub(crate) async fn run(
             .await?
             .into_interpreter();
 
-            // Install the script requirements.
-            let requirements = metadata
-                .dependencies
-                .into_iter()
-                .map(Requirement::from)
-                .collect();
-            let spec = RequirementsSpecification::from_requirements(requirements);
-            let environment = CachedEnvironment::get_or_create(
-                spec,
-                interpreter,
-                &settings,
-                &state,
-                preview,
-                connectivity,
-                concurrency,
-                native_tls,
-                cache,
-                printer.filter(show_resolution),
-            )
-            .await?;
+            // Install the script requirements, if necessary. Otherwise, use an isolated environment.
+            if let Some(dependencies) = metadata.dependencies {
+                let requirements = dependencies.into_iter().map(Requirement::from).collect();
+                let spec = RequirementsSpecification::from_requirements(requirements);
+                let environment = CachedEnvironment::get_or_create(
+                    spec,
+                    interpreter,
+                    &settings,
+                    &state,
+                    preview,
+                    connectivity,
+                    concurrency,
+                    native_tls,
+                    cache,
+                    printer.filter(show_resolution),
+                )
+                .await?;
 
-            Some(environment.into_interpreter())
+                Some(environment.into_interpreter())
+            } else {
+                // Create a virtual environment
+                temp_dir = cache.environment()?;
+                let environment = uv_virtualenv::create_venv(
+                    temp_dir.path(),
+                    interpreter,
+                    uv_virtualenv::Prompt::None,
+                    false,
+                    false,
+                    false,
+                )?;
+
+                Some(environment.into_interpreter())
+            }
         } else {
             None
         }
diff --git a/crates/uv/tests/run.rs b/crates/uv/tests/run.rs
index b3907fd4e..e4ce07b22 100644
--- a/crates/uv/tests/run.rs
+++ b/crates/uv/tests/run.rs
@@ -199,7 +199,7 @@ fn run_args() -> Result<()> {
 /// Run a PEP 723-compatible script. The script should take precedence over the workspace
 /// dependencies.
 #[test]
-fn run_script() -> Result<()> {
+fn run_pep723_script() -> Result<()> {
     let context = TestContext::new("3.12");
 
     let pyproject_toml = context.temp_dir.child("pyproject.toml");
@@ -298,6 +298,28 @@ fn run_script() -> Result<()> {
     Audited 4 packages in [TIME]
     "###);
 
+    // If the script contains a PEP 723 tag, it can omit the dependencies field.
+    let test_script = context.temp_dir.child("main.py");
+    test_script.write_str(indoc! { r#"
+        # /// script
+        # requires-python = ">=3.11"
+        # ///
+
+        print("Hello, world!")
+       "#
+    })?;
+
+    // Running the script should install the requirements.
+    uv_snapshot!(context.filters(), context.run().arg("--preview").arg("main.py"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+    Hello, world!
+
+    ----- stderr -----
+    Reading inline script metadata from: main.py
+    "###);
+
     Ok(())
 }