diff --git a/Lib/ensurepip/__init__.py b/Lib/ensurepip/__init__.py
index 3fbe8b2a5b13677..a82dbadce1635e9 100644
--- a/Lib/ensurepip/__init__.py
+++ b/Lib/ensurepip/__init__.py
@@ -90,8 +90,18 @@ def _run_pip(args, additional_paths=None):
 sys.argv[1:] = {args}
 runpy.run_module("pip", run_name="__main__", alter_sys=True)
 """
-    return subprocess.run([sys.executable, '-W', 'ignore::DeprecationWarning',
-                           "-c", code], check=True).returncode
+
+    cmd = [
+        sys.executable,
+        '-W',
+        'ignore::DeprecationWarning',
+        '-c',
+        code,
+    ]
+    if sys.flags.isolated:
+        # run code in isolated mode if currently running isolated
+        cmd.insert(1, '-I')
+    return subprocess.run(cmd, check=True).returncode
 
 
 def version():
diff --git a/Misc/NEWS.d/next/Library/2022-01-03-15-07-06.bpo-46197.Z0djv6.rst b/Misc/NEWS.d/next/Library/2022-01-03-15-07-06.bpo-46197.Z0djv6.rst
new file mode 100644
index 000000000000000..7a3b2d59dfaf42a
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2022-01-03-15-07-06.bpo-46197.Z0djv6.rst
@@ -0,0 +1 @@
+Fix :mod:`ensurepip` environment isolation for subprocess running ``pip``.