diff --git a/crates/uv/src/commands/pip/install.rs b/crates/uv/src/commands/pip/install.rs
index 44146bbea..fc5f588e4 100644
--- a/crates/uv/src/commands/pip/install.rs
+++ b/crates/uv/src/commands/pip/install.rs
@@ -236,18 +236,30 @@ pub(crate) async fn pip_install(
         if break_system_packages {
             debug!("Ignoring externally managed environment due to `--break-system-packages`");
         } else {
-            return if let Some(error) = externally_managed.into_error() {
-                Err(anyhow::anyhow!(
+            let base_message = match externally_managed.into_error() {
+                Some(error) => format!(
                     "The interpreter at {} is externally managed, and indicates the following:\n\n{}\n\nConsider creating a virtual environment with `uv venv`.",
                     environment.root().user_display().cyan(),
                     textwrap::indent(&error, "  ").green(),
-                ))
-            } else {
-                Err(anyhow::anyhow!(
+                ),
+                None => format!(
                     "The interpreter at {} is externally managed. Instead, create a virtual environment with `uv venv`.",
                     environment.root().user_display().cyan()
-                ))
+                ),
             };
+
+            let error_message = if system {
+                format!(
+                    "{}\n{}{} This happens because the `--system` flag was used, which selected the system Python interpreter.",
+                    base_message,
+                    "hint".bold().cyan(),
+                    ":".bold()
+                )
+            } else {
+                base_message
+            };
+
+            return Err(anyhow::Error::msg(error_message));
         }
     }
 
diff --git a/crates/uv/tests/it/pip_install.rs b/crates/uv/tests/it/pip_install.rs
index 7f883c364..a447d4368 100644
--- a/crates/uv/tests/it/pip_install.rs
+++ b/crates/uv/tests/it/pip_install.rs
@@ -12990,3 +12990,44 @@ fn pip_install_no_sources_editable_to_registry_switch() -> Result<()> {
 
     Ok(())
 }
+
+#[test]
+fn install_with_system_interpreter() -> Result<()> {
+    let context = TestContext::new("3.12");
+
+    // A simple requirements.txt file with pytest
+    let requirements_txt = context.temp_dir.child("requirements.txt");
+    requirements_txt.write_str("pytest")?;
+
+    // Add a custom filter to replace the system Python path
+    // works on Unix-like systems, Windows and for CPython, PyPy and GraalPy implementations
+    let filters: Vec<_> = context
+        .filters()
+        .into_iter()
+        .chain(std::iter::once((
+            r"(?:[A-Za-z]:)?([\\/]).+([\\/])python([\\/])(?:cpython|pypy|graalpy)-\d+\.\d+\.\[X\][^\s]+",
+            "[PYTHON-PATH]",
+        )))
+        .collect();
+
+    uv_snapshot!(filters, context.pip_install()
+        .arg("--system")
+        .arg("-r")
+        .arg("requirements.txt"), @r###"
+    success: false
+    exit_code: 2
+    ----- stdout -----
+    
+    ----- stderr -----
+    Using Python 3.12.[X] environment at: [PYTHON-PATH]
+    error: The interpreter at [PYTHON-PATH] is externally managed, and indicates the following:
+    
+      This Python installation is managed by uv and should not be modified.
+    
+    Consider creating a virtual environment with `uv venv`.
+    hint: This happens because the `--system` flag was used, which selected the system Python interpreter.
+    "###
+    );
+
+    Ok(())
+}