diff --git a/pkgs/development/interpreters/python/setup-hook.sh b/pkgs/development/interpreters/python/setup-hook.sh
index dda9bed39f8..35726280a75 100644
--- a/pkgs/development/interpreters/python/setup-hook.sh
+++ b/pkgs/development/interpreters/python/setup-hook.sh
@@ -19,3 +19,6 @@ envHooks+=(addPythonPath)
 export DETERMINISTIC_BUILD=1;
 # Determinism: We fix the hashes of str, bytes and datetime objects.
 export PYTHONHASHSEED=0;
+# Determinism. Whenever Python is included, it should not check user site-packages.
+# This option is only relevant when the sandbox is disabled.
+export PYTHONNOUSERSITE=1;