diff --git a/doc/source/whatsnew/v3.0.0.rst b/doc/source/whatsnew/v3.0.0.rst
index 7a4f709e56104..177a38b526c6e 100644
--- a/doc/source/whatsnew/v3.0.0.rst
+++ b/doc/source/whatsnew/v3.0.0.rst
@@ -397,7 +397,7 @@ Missing
 
 MultiIndex
 ^^^^^^^^^^
--
+- :func:`DataFrame.loc` with ``axis=0``  and :class:`MultiIndex` when setting a value adds extra columns (:issue:`58116`)
 -
 
 I/O
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index c9b502add21e0..b3ae53272cae4 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -757,7 +757,7 @@ def _get_setitem_indexer(self, key):
         """
         if self.name == "loc":
             # always holds here bc iloc overrides _get_setitem_indexer
-            self._ensure_listlike_indexer(key)
+            self._ensure_listlike_indexer(key, axis=self.axis)
 
         if isinstance(key, tuple):
             for x in key:
@@ -857,8 +857,10 @@ def _ensure_listlike_indexer(self, key, axis=None, value=None) -> None:
         if isinstance(key, tuple) and len(key) > 1:
             # key may be a tuple if we are .loc
             # if length of key is > 1 set key to column part
-            key = key[column_axis]
-            axis = column_axis
+            # unless axis is already specified, then go with that
+            if axis is None:
+                axis = column_axis
+            key = key[axis]
 
         if (
             axis == column_axis
diff --git a/pandas/tests/indexing/multiindex/test_loc.py b/pandas/tests/indexing/multiindex/test_loc.py
index 67b9ddebfb8bf..d482d20591a8a 100644
--- a/pandas/tests/indexing/multiindex/test_loc.py
+++ b/pandas/tests/indexing/multiindex/test_loc.py
@@ -381,6 +381,29 @@ def test_multiindex_setitem_columns_enlarging(self, indexer, exp_value):
         )
         tm.assert_frame_equal(df, expected)
 
+    def test_multiindex_setitem_axis_set(self):
+        # GH#58116
+        dates = pd.date_range("2001-01-01", freq="D", periods=2)
+        ids = ["i1", "i2", "i3"]
+        index = MultiIndex.from_product([dates, ids], names=["date", "identifier"])
+        df = DataFrame(0.0, index=index, columns=["A", "B"])
+        df.loc(axis=0)["2001-01-01", ["i1", "i3"]] = None
+
+        expected = DataFrame(
+            [
+                [None, None],
+                [0.0, 0.0],
+                [None, None],
+                [0.0, 0.0],
+                [0.0, 0.0],
+                [0.0, 0.0],
+            ],
+            index=index,
+            columns=["A", "B"],
+        )
+
+        tm.assert_frame_equal(df, expected)
+
     def test_sorted_multiindex_after_union(self):
         # GH#44752
         midx = MultiIndex.from_product(