diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 6de83e34122c2..492424255bcf2 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -2768,3 +2768,19 @@ def test_loc_setitem_dict_timedelta_multiple_set(self):
             [[Timedelta(6, unit="s"), "foo"]], columns=["time", "value"], index=[1]
         )
         tm.assert_frame_equal(result, expected)
+
+    def test_loc_set_multiple_items_in_multiple_new_columns(self):
+        # GH 25594
+        df = DataFrame(index=[1, 2], columns=["a"])
+        df.loc[1, ["b", "c"]] = [6, 7]
+
+        expected = DataFrame(
+            {
+                "a": Series([np.nan, np.nan], dtype="object"),
+                "b": [6, np.nan],
+                "c": [7, np.nan],
+            },
+            index=[1, 2],
+        )
+
+        tm.assert_frame_equal(df, expected)