diff --git a/doc/source/whatsnew/v1.5.1.rst b/doc/source/whatsnew/v1.5.1.rst
index 6690f067956a0..e5a7f6529e383 100644
--- a/doc/source/whatsnew/v1.5.1.rst
+++ b/doc/source/whatsnew/v1.5.1.rst
@@ -72,6 +72,7 @@ Fixed regressions
 - Fixed Regression in :meth:`Series.__setitem__` casting ``None`` to ``NaN`` for object dtype (:issue:`48665`)
 - Fixed Regression in :meth:`DataFrame.loc` when setting values as a :class:`DataFrame` with all ``True`` indexer (:issue:`48701`)
 - Regression in :func:`.read_csv` causing an ``EmptyDataError`` when using an UTF-8 file handle that was already read from (:issue:`48646`)
+- Fixed regression in :meth:`DataFrame.loc` raising ``FutureWarning`` when setting an empty :class:`DataFrame` (:issue:`48480`)
 - Fixed regression in :meth:`DataFrame.describe` raising ``TypeError`` when result contains ``NA`` (:issue:`48778`)
 - Fixed regression in :meth:`DataFrame.plot` ignoring invalid ``colormap`` for ``kind="scatter"`` (:issue:`48726`)
 - Fixed performance regression in :func:`factorize` when ``na_sentinel`` is not ``None`` and ``sort=False`` (:issue:`48620`)
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 08461b47b4c80..464cb3f07df33 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -2002,7 +2002,7 @@ def _setitem_single_column(self, loc: int, value, plane_indexer):
 
         new_values = self.obj._get_column_array(loc)
 
-        if can_hold_element(orig_values, new_values):
+        if can_hold_element(orig_values, new_values) and not len(new_values) == 0:
             # Don't issue the warning yet, as we can still trim a few cases where
             #  behavior will not change.
 
diff --git a/pandas/tests/frame/indexing/test_indexing.py b/pandas/tests/frame/indexing/test_indexing.py
index 3062dff27d537..acd742c54b908 100644
--- a/pandas/tests/frame/indexing/test_indexing.py
+++ b/pandas/tests/frame/indexing/test_indexing.py
@@ -1414,6 +1414,15 @@ def test_loc_setitem_reordering_with_all_true_indexer(self, col):
         df.loc[n * [True], ["x", "y"]] = df[["x", "y"]]
         tm.assert_frame_equal(df, expected)
 
+    def test_loc_rhs_empty_warning(self):
+        # GH48480
+        df = DataFrame(columns=["a", "b"])
+        expected = df.copy()
+        rhs = DataFrame(columns=["a"])
+        with tm.assert_produces_warning(None):
+            df.loc[:, "a"] = rhs
+        tm.assert_frame_equal(df, expected)
+
 
 class TestDataFrameIndexingUInt64:
     def test_setitem(self, uint64_frame):
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 4e5571c7087e7..e62fb98b0782d 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -600,8 +600,7 @@ def test_loc_setitem_consistency_empty(self):
         expected = DataFrame(columns=["x", "y"])
         expected["x"] = expected["x"].astype(np.int64)
         df = DataFrame(columns=["x", "y"])
-        msg = "will attempt to set the values inplace instead"
-        with tm.assert_produces_warning(FutureWarning, match=msg):
+        with tm.assert_produces_warning(None):
             df.loc[:, "x"] = 1
         tm.assert_frame_equal(df, expected)