diff --git a/pandas/core/internals/array_manager.py b/pandas/core/internals/array_manager.py
index f2cd6320d885a..157e90d6e8b0a 100644
--- a/pandas/core/internals/array_manager.py
+++ b/pandas/core/internals/array_manager.py
@@ -1281,6 +1281,14 @@ def apply(self, func, **kwargs):
         return type(self)([new_array], self._axes)
 
     def setitem(self, indexer, value):
+        """
+        Set values with indexer.
+
+        For SingleArrayManager, this backs s[indexer] = value
+
+        See `setitem_inplace` for a version that works inplace and doesn't
+        return a new Manager.
+        """
         return self.apply_with_block("setitem", indexer=indexer, value=value)
 
     def idelete(self, indexer) -> SingleArrayManager:
diff --git a/pandas/core/internals/base.py b/pandas/core/internals/base.py
index e65318dd29c52..4d3dcb9c4732e 100644
--- a/pandas/core/internals/base.py
+++ b/pandas/core/internals/base.py
@@ -159,6 +159,18 @@ def array(self):
         """
         return self.arrays[0]  # type: ignore[attr-defined]
 
+    def setitem_inplace(self, indexer, value) -> None:
+        """
+        Set values with indexer.
+
+        For Single[Block/Array]Manager, this backs s[indexer] = value
+
+        This is an inplace version of `setitem()`, mutating the manager/values
+        in place, not returning a new Manager (and Block), and thus never changing
+        the dtype.
+        """
+        self.array[indexer] = value
+
 
 def interleaved_dtype(dtypes: list[DtypeObj]) -> DtypeObj | None:
     """
diff --git a/pandas/core/internals/managers.py b/pandas/core/internals/managers.py
index 9d35e1e8d4929..7c8b289e6eb87 100644
--- a/pandas/core/internals/managers.py
+++ b/pandas/core/internals/managers.py
@@ -352,6 +352,11 @@ def where(self: T, other, cond, align: bool, errors: str) -> T:
         )
 
     def setitem(self: T, indexer, value) -> T:
+        """
+        Set values with indexer.
+
+        For SingleBlockManager, this backs s[indexer] = value
+        """
         return self.apply("setitem", indexer=indexer, value=value)
 
     def putmask(self, mask, new, align: bool = True):
diff --git a/pandas/core/series.py b/pandas/core/series.py
index ce986f2dd8038..6efd1f65c2264 100644
--- a/pandas/core/series.py
+++ b/pandas/core/series.py
@@ -1061,7 +1061,6 @@ def __setitem__(self, key, value) -> None:
         try:
             self._set_with_engine(key, value)
         except (KeyError, ValueError):
-            values = self._values
             if is_integer(key) and self.index.inferred_type != "integer":
                 # positional setter
                 if not self.index._should_fallback_to_positional:
@@ -1075,7 +1074,8 @@ def __setitem__(self, key, value) -> None:
                         FutureWarning,
                         stacklevel=2,
                     )
-                values[key] = value
+                # this is equivalent to self._values[key] = value
+                self._mgr.setitem_inplace(key, value)
             else:
                 # GH#12862 adding a new key to the Series
                 self.loc[key] = value
@@ -1107,7 +1107,8 @@ def _set_with_engine(self, key, value) -> None:
         # error: Argument 1 to "validate_numeric_casting" has incompatible type
         # "Union[dtype, ExtensionDtype]"; expected "dtype"
         validate_numeric_casting(self.dtype, value)  # type: ignore[arg-type]
-        self._values[loc] = value
+        # this is equivalent to self._values[key] = value
+        self._mgr.setitem_inplace(loc, value)
 
     def _set_with(self, key, value):
         # other: fancy integer or otherwise