diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 08bd3cde60806..675e5145c5856 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -2353,7 +2353,6 @@ def ravel(i):
                 return i.ravel() if isinstance(i, np.ndarray) else i
 
             indexer = tuple(map(ravel, indexer))
-
             aligners = [not com.is_null_slice(idx) for idx in indexer]
             sum_aligners = sum(aligners)
             single_aligner = sum_aligners == 1
@@ -2371,7 +2370,9 @@ def ravel(i):
 
             # we have a frame, with multiple indexers on both axes; and a
             # series, so need to broadcast (see GH5206)
-            if sum_aligners == self.ndim and all(is_sequence(_) for _ in indexer):
+            if len(indexer) == self.ndim and all(
+                is_sequence(_) or isinstance(_, slice) for _ in indexer
+            ):
                 ser_values = ser.reindex(obj.axes[0][indexer[0]])._values
 
                 # single indexer
@@ -2399,7 +2400,6 @@ def ravel(i):
                         if using_cow:
                             return ser
                         return ser._values.copy()
-
                     return ser.reindex(new_ix)._values
 
                 # 2 dims
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 36b08ee1df790..643a5e126bb34 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -3297,3 +3297,36 @@ def test_loc_reindexing_of_empty_index(self):
         df.loc[Series([False] * 4, index=df.index, name=0), 0] = df[0]
         expected = DataFrame(index=[1, 1, 2, 2], data=["1", "1", "2", "2"])
         tm.assert_frame_equal(df, expected)
+
+    def test_loc_set_series_to_multiple_columns(self):
+        # GH 59933
+        df = DataFrame([[1, 2, 3], [4, 5, 6]], columns=list("ABC"))
+        df.loc[0:3, ["A", "B", "C"]] = Series([10, 20, 30])
+        expected = DataFrame([[10, 10, 10], [20, 20, 20]], columns=list("ABC"))
+        tm.assert_frame_equal(df, expected)
+
+        df = DataFrame([[1, 2, 3], [4, 5, 6]], columns=list("ABC"))
+        df.loc[:, ["A", "B", "C"]] = Series([10, 20, 30])
+        expected = DataFrame([[10, 10, 10], [20, 20, 20]], columns=list("ABC"))
+        tm.assert_frame_equal(df, expected)
+
+        df = DataFrame([[1, 2, 3], [4, 5, 6], [7, 8, 9]], columns=list("ABC"))
+        df.loc[df["A"] > 0, ["A", "B", "C"]] = Series([10, 20, 30])
+        expected = DataFrame(
+            [[10, 10, 10], [20, 20, 20], [30, 30, 30]], columns=list("ABC")
+        )
+        tm.assert_frame_equal(df, expected)
+
+        df = DataFrame([[1, 2, 3], [4, 5, 6], [7, 8, 9]], columns=list("ABC"))
+        df.loc[:, ["A", "B", "C"]] = Series([10, 20, 30])
+        expected = DataFrame(
+            [[10, 10, 10], [20, 20, 20], [30, 30, 30]], columns=list("ABC")
+        )
+        tm.assert_frame_equal(df, expected)
+
+        df = DataFrame([[1, 2, 3], [4, 5, 6], [7, 8, 9]], columns=list("ABC"))
+        df.loc[0:4, ["A", "B", "C"]] = Series([10, 20, 30])
+        expected = DataFrame(
+            [[10, 10, 10], [20, 20, 20], [30, 30, 30]], columns=list("ABC")
+        )
+        tm.assert_frame_equal(df, expected)