diff --git a/Misc/NEWS.d/next/Core_and_Builtins/2025-06-11-21-40-21.gh-issue-135385.e2TFON.rst b/Misc/NEWS.d/next/Core_and_Builtins/2025-06-11-21-40-21.gh-issue-135385.e2TFON.rst
new file mode 100644
index 00000000000000..99824404dfd7f4
--- /dev/null
+++ b/Misc/NEWS.d/next/Core_and_Builtins/2025-06-11-21-40-21.gh-issue-135385.e2TFON.rst
@@ -0,0 +1,2 @@
+Fix a memory regression for classes that have both :attr:`~object.__slots__` and
+:attr:`~object.__dict__`.
diff --git a/Objects/typeobject.c b/Objects/typeobject.c
index db923c164774b7..1e974669ba20a7 100644
--- a/Objects/typeobject.c
+++ b/Objects/typeobject.c
@@ -4621,7 +4621,19 @@ type_new_descriptors(const type_new_ctx *ctx, PyTypeObject *type)
     }
 
     type->tp_basicsize = slotoffset;
-    type->tp_itemsize = ctx->base->tp_itemsize;
+
+    // Only inherit tp_itemsize if this type defines its own __slots__
+    // Classes that don't define __slots__ but inherit from __slots__ classes
+    // should not inherit tp_itemsize as they don't use variable-size items
+    if (et->ht_slots != NULL && PyTuple_GET_SIZE(et->ht_slots) > 0) {
+        // This type defines its own __slots__, inherit tp_itemsize
+        type->tp_itemsize = ctx->base->tp_itemsize;
+    }
+    else {
+        // This type doesn't define __slots__, don't inherit tp_itemsize
+        type->tp_itemsize = 0;
+    }
+
     type->tp_members = _PyHeapType_GET_MEMBERS(et);
     return 0;
 }