diff --git a/pandas/io/formats/excel.py b/pandas/io/formats/excel.py
index 98f7b64d2cda0..f11127eb97dd9 100644
--- a/pandas/io/formats/excel.py
+++ b/pandas/io/formats/excel.py
@@ -647,7 +647,9 @@ def _format_header_mi(self) -> Iterable[ExcelCell]:
             for lnum, (spans, levels, level_codes) in enumerate(
                 zip(level_lengths, columns.levels, columns.codes)
             ):
-                values = levels.take(level_codes)
+                values = levels.take(
+                    level_codes, fill_value=self.na_rep if -1 in level_codes else None
+                )
                 for i, span_val in spans.items():
                     mergestart, mergeend = None, None
                     if span_val > 1:
diff --git a/pandas/tests/io/excel/test_writers.py b/pandas/tests/io/excel/test_writers.py
index 9a8e4eff5470a..6c27daf3d56ca 100644
--- a/pandas/tests/io/excel/test_writers.py
+++ b/pandas/tests/io/excel/test_writers.py
@@ -792,6 +792,28 @@ def test_to_excel_multiindex_cols(self, merge_cells, frame, path):
             frame.columns = [".".join(map(str, q)) for q in zip(*fm)]
         tm.assert_frame_equal(frame, df)
 
+    @pytest.mark.xfail(reason="na_values aren't applied to Index")
+    def test_to_excel_multiindex_nan_level(self, frame, path):
+        """
+        Tests https://github.com/pandas-dev/pandas/issues/51252
+        """
+        cols_index = MultiIndex.from_tuples(
+            [
+                ("Item", "Type 1", "Class A"),
+                ("Item", "Type 1", "Class B"),
+                ("Item", "Type 2", "Class A"),
+                ("Item", "Type 2", "Class B"),
+                ("Item", "Type 3", None),
+            ]
+        )
+        df = pd.DataFrame(np.random.randn(10, 5), columns=cols_index)
+        df.to_excel(path, "test1")
+        with ExcelFile(path) as reader:
+            df2 = pd.read_excel(
+                reader, sheet_name="test1", header=[0, 1, 2], index_col=[0]
+            )
+        tm.assert_frame_equal(df, df2)
+
     def test_to_excel_multiindex_dates(self, merge_cells, tsframe, path):
         # try multiindex with dates
         new_index = [tsframe.index, np.arange(len(tsframe.index), dtype=np.int64)]