diff --git a/doc/source/whatsnew/v1.3.0.rst b/doc/source/whatsnew/v1.3.0.rst
index dca31641a4634..74510d91db871 100644
--- a/doc/source/whatsnew/v1.3.0.rst
+++ b/doc/source/whatsnew/v1.3.0.rst
@@ -289,6 +289,7 @@ Indexing
 - Bug in :meth:`DataFrame.loc.__setitem__` raising ValueError when expanding unique column for :class:`DataFrame` with duplicate columns (:issue:`38521`)
 - Bug in :meth:`DataFrame.iloc.__setitem__` and :meth:`DataFrame.loc.__setitem__` with mixed dtypes when setting with a dictionary value (:issue:`38335`)
 - Bug in :meth:`DataFrame.__setitem__` not raising ``ValueError`` when right hand side is a :class:`DataFrame` with wrong number of columns (:issue:`38604`)
+- Bug in :meth:`Series.__setitem__` raising ``ValueError`` when setting a :class:`Series` with a scalar indexer (:issue:`38303`)
 - Bug in :meth:`DataFrame.loc` dropping levels of :class:`MultiIndex` when :class:`DataFrame` used as input has only one row (:issue:`10521`)
 - Bug in :meth:`DataFrame.__getitem__` and :meth:`Series.__getitem__` always raising ``KeyError`` when slicing with existing strings an :class:`Index` with milliseconds (:issue:`33589`)
 - Bug in setting ``timedelta64`` values into numeric :class:`Series` failing to cast to object dtype (:issue:`39086`)
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 998a34ce834ea..d7ff34ac774fe 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -2023,7 +2023,17 @@ def ravel(i):
                         return ser._values.copy()
                     return ser.reindex(ax)._values
 
-        elif is_scalar(indexer):
+        elif is_integer(indexer) and self.ndim == 1:
+            if is_object_dtype(self.obj):
+                return ser
+            ax = self.obj._get_axis(0)
+
+            if ser.index.equals(ax):
+                return ser._values.copy()
+
+            return ser.reindex(ax)._values[indexer]
+
+        elif is_integer(indexer):
             ax = self.obj._get_axis(1)
 
             if ser.index.equals(ax):
diff --git a/pandas/tests/series/indexing/test_setitem.py b/pandas/tests/series/indexing/test_setitem.py
index 7f469f361fec7..c53e2ba31aba0 100644
--- a/pandas/tests/series/indexing/test_setitem.py
+++ b/pandas/tests/series/indexing/test_setitem.py
@@ -93,6 +93,24 @@ def test_setitem_negative_out_of_bounds(self):
         with pytest.raises(IndexError, match=msg):
             ser[-11] = "foo"
 
+    @pytest.mark.parametrize("indexer", [tm.loc, tm.at])
+    @pytest.mark.parametrize("ser_index", [0, 1])
+    def test_setitem_series_object_dtype(self, indexer, ser_index):
+        # GH#38303
+        ser = Series([0, 0], dtype="object")
+        idxr = indexer(ser)
+        idxr[0] = Series([42], index=[ser_index])
+        expected = Series([Series([42], index=[ser_index]), 0], dtype="object")
+        tm.assert_series_equal(ser, expected)
+
+    @pytest.mark.parametrize("index, exp_value", [(0, 42.0), (1, np.nan)])
+    def test_setitem_series(self, index, exp_value):
+        # GH#38303
+        ser = Series([0, 0])
+        ser.loc[0] = Series([42], index=[index])
+        expected = Series([exp_value, 0])
+        tm.assert_series_equal(ser, expected)
+
 
 class TestSetitemSlices:
     def test_setitem_slice_float_raises(self, datetime_series):