diff --git a/Cargo.lock b/Cargo.lock
index cd650bede..63dedc89e 100644
--- a/Cargo.lock
+++ b/Cargo.lock
@@ -5456,6 +5456,7 @@ dependencies = [
  "schemars",
  "serde",
  "serde_json",
+ "sys-info",
  "target-lexicon",
  "temp-env",
  "tempfile",
diff --git a/crates/uv-python/Cargo.toml b/crates/uv-python/Cargo.toml
index 7b9b98d6b..0a26279f9 100644
--- a/crates/uv-python/Cargo.toml
+++ b/crates/uv-python/Cargo.toml
@@ -51,6 +51,7 @@ same-file = { workspace = true }
 schemars = { workspace = true, optional = true }
 serde = { workspace = true, features = ["derive"] }
 serde_json = { workspace = true }
+sys-info = { workspace = true }
 target-lexicon = { workspace = true }
 tempfile = { workspace = true }
 thiserror = { workspace = true }
diff --git a/crates/uv-python/src/interpreter.rs b/crates/uv-python/src/interpreter.rs
index 417d094ee..228bad505 100644
--- a/crates/uv-python/src/interpreter.rs
+++ b/crates/uv-python/src/interpreter.rs
@@ -848,9 +848,13 @@ impl InterpreterInfo {
 
         let cache_entry = cache.entry(
             CacheBucket::Interpreter,
-            // Shard interpreter metadata by host architecture, to avoid cache collisions when
-            // running universal binaries under Rosetta.
-            ARCH,
+            // Shard interpreter metadata by host architecture, operating system, and version, to
+            // invalidate the cache (e.g.) on OS upgrades.
+            cache_digest(&(
+                ARCH,
+                sys_info::os_type().unwrap_or_default(),
+                sys_info::os_release().unwrap_or_default(),
+            )),
             // We use the absolute path for the cache entry to avoid cache collisions for relative
             // paths. But we don't to query the executable with symbolic links resolved.
             format!("{}.msgpack", cache_digest(&absolute)),