diff --git a/pandas/core/series.py b/pandas/core/series.py
index 8381c405fbd3d..e94689383100d 100644
--- a/pandas/core/series.py
+++ b/pandas/core/series.py
@@ -1061,6 +1061,10 @@ def __setitem__(self, key, value) -> None:
         if key is Ellipsis:
             key = slice(None)
 
+        if isinstance(key, slice):
+            indexer = self.index._convert_slice_indexer(key, kind="getitem")
+            return self._set_values(indexer, value)
+
         try:
             self._set_with_engine(key, value)
         except (KeyError, ValueError):
@@ -1074,6 +1078,7 @@ def __setitem__(self, key, value) -> None:
 
         except (InvalidIndexError, TypeError) as err:
             if isinstance(key, tuple) and not isinstance(self.index, MultiIndex):
+                # cases with MultiIndex don't get here bc they raise KeyError
                 raise KeyError(
                     "key of type tuple not found and not a MultiIndex"
                 ) from err
@@ -1102,34 +1107,25 @@ def _set_with_engine(self, key, value) -> None:
 
     def _set_with(self, key, value):
         # other: fancy integer or otherwise
-        if isinstance(key, slice):
-            indexer = self.index._convert_slice_indexer(key, kind="getitem")
-            return self._set_values(indexer, value)
-
-        else:
-            assert not isinstance(key, tuple)
+        assert not isinstance(key, tuple)
 
-            if is_scalar(key):
-                key = [key]
-            elif is_iterator(key):
-                # Without this, the call to infer_dtype will consume the generator
-                key = list(key)
+        if is_scalar(key):
+            key = [key]
+        elif is_iterator(key):
+            # Without this, the call to infer_dtype will consume the generator
+            key = list(key)
 
-            if isinstance(key, Index):
-                key_type = key.inferred_type
-                key = key._values
-            else:
-                key_type = lib.infer_dtype(key, skipna=False)
+        key_type = lib.infer_dtype(key, skipna=False)
 
-            # Note: key_type == "boolean" should not occur because that
-            #  should be caught by the is_bool_indexer check in __setitem__
-            if key_type == "integer":
-                if not self.index._should_fallback_to_positional:
-                    self._set_labels(key, value)
-                else:
-                    self._set_values(key, value)
+        # Note: key_type == "boolean" should not occur because that
+        #  should be caught by the is_bool_indexer check in __setitem__
+        if key_type == "integer":
+            if not self.index._should_fallback_to_positional:
+                self._set_labels(key, value)
             else:
-                self.loc[key] = value
+                self._set_values(key, value)
+        else:
+            self.loc[key] = value
 
     def _set_labels(self, key, value) -> None:
         key = com.asarray_tuplesafe(key)
@@ -1140,7 +1136,7 @@ def _set_labels(self, key, value) -> None:
         self._set_values(indexer, value)
 
     def _set_values(self, key, value) -> None:
-        if isinstance(key, Series):
+        if isinstance(key, (Index, Series)):
             key = key._values
 
         self._mgr = self._mgr.setitem(indexer=key, value=value)