diff --git a/pkgs/development/python-modules/httpx/default.nix b/pkgs/development/python-modules/httpx/default.nix
index 3d0041508d8f..e63970de3118 100644
--- a/pkgs/development/python-modules/httpx/default.nix
+++ b/pkgs/development/python-modules/httpx/default.nix
@@ -108,6 +108,10 @@ buildPythonPackage rec {
 
   __darwinAllowLocalNetworking = true;
 
+  # stdenv's fake SSL_CERT_FILE breaks default http transport constructor with:
+  # FileNotFoundError: [Errno 2] No such file or directory
+  setupHook = ./setup-hook.sh;
+
   meta = with lib; {
     changelog = "https://github.com/encode/httpx/blob/${src.rev}/CHANGELOG.md";
     description = "Next generation HTTP client";
diff --git a/pkgs/development/python-modules/httpx/setup-hook.sh b/pkgs/development/python-modules/httpx/setup-hook.sh
new file mode 100644
index 000000000000..7e9ced07b69c
--- /dev/null
+++ b/pkgs/development/python-modules/httpx/setup-hook.sh
@@ -0,0 +1,5 @@
+httpxSslCertFileUnset() {
+    unset SSL_CERT_FILE
+}
+
+postHooks+=(httpxSslCertFileUnset)