diff --git a/doc/source/whatsnew/v1.5.3.rst b/doc/source/whatsnew/v1.5.3.rst
index e0bcd81805cc1..cf079f43f6457 100644
--- a/doc/source/whatsnew/v1.5.3.rst
+++ b/doc/source/whatsnew/v1.5.3.rst
@@ -14,6 +14,7 @@ including other versions of pandas.
 Fixed regressions
 ~~~~~~~~~~~~~~~~~
 - Fixed performance regression in :meth:`Series.isin` when ``values`` is empty (:issue:`49839`)
+- Fixed regression in :meth:`DataFrame.memory_usage` showing unnecessary ``FutureWarning`` when :class:`DataFrame` is empty (:issue:`50066`)
 - Fixed regression in :meth:`DataFrameGroupBy.transform` when used with ``as_index=False`` (:issue:`49834`)
 - Enforced reversion of ``color`` as an alias for ``c`` and ``size`` as an alias for ``s`` in function :meth:`DataFrame.plot.scatter` (:issue:`49732`)
 - Fixed regression in :meth:`SeriesGroupBy.apply` setting a ``name`` attribute on the result if the result was a :class:`DataFrame` (:issue:`49907`)
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 84d45b9e105c2..4bced8f93e3ea 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -3552,6 +3552,7 @@ def memory_usage(self, index: bool = True, deep: bool = False) -> Series:
         result = self._constructor_sliced(
             [c.memory_usage(index=False, deep=deep) for col, c in self.items()],
             index=self.columns,
+            dtype=np.intp,
         )
         if index:
             index_memory_usage = self._constructor_sliced(
diff --git a/pandas/tests/io/formats/test_info.py b/pandas/tests/io/formats/test_info.py
index 54b5e699cd034..1657327dd7344 100644
--- a/pandas/tests/io/formats/test_info.py
+++ b/pandas/tests/io/formats/test_info.py
@@ -20,6 +20,7 @@
     date_range,
     option_context,
 )
+import pandas._testing as tm
 
 
 @pytest.fixture
@@ -491,3 +492,12 @@ def test_info_int_columns():
         """
     )
     assert result == expected
+
+
+def test_memory_usage_empty_no_warning():
+    # GH#50066
+    df = DataFrame(index=["a", "b"])
+    with tm.assert_produces_warning(None):
+        result = df.memory_usage()
+    expected = Series(16 if IS64 else 8, index=["Index"])
+    tm.assert_series_equal(result, expected)