diff --git a/pandas/tests/copy_view/test_methods.py b/pandas/tests/copy_view/test_methods.py
index ae5ffb98558d3..d822cc03c499d 100644
--- a/pandas/tests/copy_view/test_methods.py
+++ b/pandas/tests/copy_view/test_methods.py
@@ -1359,6 +1359,33 @@ def test_isetitem(using_copy_on_write):
         assert not np.shares_memory(get_array(df, "c"), get_array(df2, "c"))
 
 
+@pytest.mark.parametrize(
+    "dtype", ["int64", "float64"], ids=["single-block", "mixed-block"]
+)
+def test_isetitem_series(using_copy_on_write, dtype):
+    df = DataFrame({"a": [1, 2, 3], "b": np.array([4, 5, 6], dtype=dtype)})
+    ser = Series([7, 8, 9])
+    ser_orig = ser.copy()
+    df.isetitem(0, ser)
+
+    if using_copy_on_write:
+        # TODO(CoW) this can share memory
+        assert not np.shares_memory(get_array(df, "a"), get_array(ser))
+
+    # mutating dataframe doesn't update series
+    df.loc[0, "a"] = 0
+    tm.assert_series_equal(ser, ser_orig)
+
+    # mutating series doesn't update dataframe
+    df = DataFrame({"a": [1, 2, 3], "b": np.array([4, 5, 6], dtype=dtype)})
+    ser = Series([7, 8, 9])
+    df.isetitem(0, ser)
+
+    ser.loc[0] = 0
+    expected = DataFrame({"a": [7, 8, 9], "b": np.array([4, 5, 6], dtype=dtype)})
+    tm.assert_frame_equal(df, expected)
+
+
 @pytest.mark.parametrize("key", ["a", ["a"]])
 def test_get(using_copy_on_write, key):
     df = DataFrame({"a": [1, 2, 3], "b": [4, 5, 6]})