diff --git a/doc/source/whatsnew/v1.1.4.rst b/doc/source/whatsnew/v1.1.4.rst
index 6cb728800dc68..7d35e8b12b9b8 100644
--- a/doc/source/whatsnew/v1.1.4.rst
+++ b/doc/source/whatsnew/v1.1.4.rst
@@ -28,6 +28,7 @@ Fixed regressions
 - Fixed regression in certain offsets (:meth:`pd.offsets.Day() <pandas.tseries.offsets.Day>` and below) no longer being hashable (:issue:`37267`)
 - Fixed regression in :class:`StataReader` which required ``chunksize`` to be manually set when using an iterator to read a dataset (:issue:`37280`)
 - Fixed regression in setitem with :meth:`DataFrame.iloc` which raised error when trying to set a value while filtering with a boolean list (:issue:`36741`)
+- Fixed regression in setitem with a Series getting aligned before setting the values (:issue:`37427`)
 - Fixed regression in :attr:`MultiIndex.is_monotonic_increasing` returning wrong results with ``NaN`` in at least one of the levels (:issue:`37220`)
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/series.py b/pandas/core/series.py
index 379c4ac1c9526..2cd861cc11b28 100644
--- a/pandas/core/series.py
+++ b/pandas/core/series.py
@@ -1048,10 +1048,8 @@ def _set_with_engine(self, key, value):
     def _set_with(self, key, value):
         # other: fancy integer or otherwise
         if isinstance(key, slice):
-            # extract_array so that if we set e.g. ser[-5:] = ser[:5]
-            #  we get the first five values, and not 5 NaNs
             indexer = self.index._convert_slice_indexer(key, kind="getitem")
-            self.iloc[indexer] = extract_array(value, extract_numpy=True)
+            return self._set_values(indexer, value)
 
         else:
             assert not isinstance(key, tuple)
@@ -1069,12 +1067,28 @@ def _set_with(self, key, value):
             #  should be caught by the is_bool_indexer check in __setitem__
             if key_type == "integer":
                 if not self.index._should_fallback_to_positional():
-                    self.loc[key] = value
+                    self._set_labels(key, value)
                 else:
-                    self.iloc[key] = value
+                    self._set_values(key, value)
             else:
                 self.loc[key] = value
 
+    def _set_labels(self, key, value):
+        key = com.asarray_tuplesafe(key)
+        indexer: np.ndarray = self.index.get_indexer(key)
+        mask = indexer == -1
+        if mask.any():
+            raise KeyError(f"{key[mask]} not in index")
+        self._set_values(indexer, value)
+
+    def _set_values(self, key, value):
+        if isinstance(key, Series):
+            key = key._values
+        self._mgr = self._mgr.setitem(  # type: ignore[assignment]
+            indexer=key, value=value
+        )
+        self._maybe_update_cacher()
+
     def _set_value(self, label, value, takeable: bool = False):
         """
         Quickly set single value at passed label.
diff --git a/pandas/tests/series/indexing/test_getitem.py b/pandas/tests/series/indexing/test_getitem.py
index 9f6aab823c3ad..cc448279bfce0 100644
--- a/pandas/tests/series/indexing/test_getitem.py
+++ b/pandas/tests/series/indexing/test_getitem.py
@@ -290,3 +290,13 @@ def test_getitem_multilevel_scalar_slice_not_implemented(
     msg = r"\(2000, slice\(3, 4, None\)\)"
     with pytest.raises(TypeError, match=msg):
         ser[2000, 3:4]
+
+
+def test_getitem_assignment_series_aligment():
+    # https://github.com/pandas-dev/pandas/issues/37427
+    # with getitem, when assigning with a Series, it is not first aligned
+    s = Series(range(10))
+    idx = np.array([2, 4, 9])
+    s[idx] = Series([10, 11, 12])
+    expected = Series([0, 1, 10, 3, 11, 5, 6, 7, 8, 12])
+    tm.assert_series_equal(s, expected)