diff --git a/doc/source/whatsnew/v2.1.0.rst b/doc/source/whatsnew/v2.1.0.rst
index a949ec808c5cd..762f41b4049c2 100644
--- a/doc/source/whatsnew/v2.1.0.rst
+++ b/doc/source/whatsnew/v2.1.0.rst
@@ -14,10 +14,12 @@ including other versions of pandas.
 Enhancements
 ~~~~~~~~~~~~
 
-.. _whatsnew_210.enhancements.enhancement1:
+.. _whatsnew_210.enhancements.cow:
 
-enhancement1
-^^^^^^^^^^^^
+Copy-on-Write improvements
+^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+- Setting a :class:`Series` into a :class:`DataFrame` now creates a lazy instead of a deep copy (:issue:`53142`)
 
 .. _whatsnew_210.enhancements.enhancement2:
 
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 3e6c89139d06d..bf91a52163569 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -3915,7 +3915,6 @@ def isetitem(self, loc, value) -> None:
         In cases where ``frame.columns`` is unique, this is equivalent to
         ``frame[frame.columns[i]] = value``.
         """
-        using_cow = using_copy_on_write()
         if isinstance(value, DataFrame):
             if is_integer(loc):
                 loc = [loc]
@@ -3927,13 +3926,11 @@ def isetitem(self, loc, value) -> None:
                 )
 
             for i, idx in enumerate(loc):
-                arraylike, refs = self._sanitize_column(
-                    value.iloc[:, i], using_cow=using_cow
-                )
+                arraylike, refs = self._sanitize_column(value.iloc[:, i])
                 self._iset_item_mgr(idx, arraylike, inplace=False, refs=refs)
             return
 
-        arraylike, refs = self._sanitize_column(value, using_cow=using_cow)
+        arraylike, refs = self._sanitize_column(value)
         self._iset_item_mgr(loc, arraylike, inplace=False, refs=refs)
 
     def __setitem__(self, key, value):
@@ -4170,7 +4167,7 @@ def _set_item(self, key, value) -> None:
         Series/TimeSeries will be conformed to the DataFrames index to
         ensure homogeneity.
         """
-        value, refs = self._sanitize_column(value, using_cow=using_copy_on_write())
+        value, refs = self._sanitize_column(value)
 
         if (
             key in self.columns
@@ -4813,7 +4810,7 @@ def insert(
         elif isinstance(value, DataFrame):
             value = value.iloc[:, 0]
 
-        value, refs = self._sanitize_column(value, using_cow=using_copy_on_write())
+        value, refs = self._sanitize_column(value)
         self._mgr.insert(loc, column, value, refs=refs)
 
     def assign(self, **kwargs) -> DataFrame:
@@ -4884,9 +4881,7 @@ def assign(self, **kwargs) -> DataFrame:
             data[k] = com.apply_if_callable(v, data)
         return data
 
-    def _sanitize_column(
-        self, value, using_cow: bool = False
-    ) -> tuple[ArrayLike, BlockValuesRefs | None]:
+    def _sanitize_column(self, value) -> tuple[ArrayLike, BlockValuesRefs | None]:
         """
         Ensures new columns (which go into the BlockManager as new blocks) are
         always copied (or a reference is being tracked to them under CoW)
@@ -4907,7 +4902,7 @@ def _sanitize_column(
         if is_dict_like(value):
             if not isinstance(value, Series):
                 value = Series(value)
-            return _reindex_for_setitem(value, self.index, using_cow=using_cow)
+            return _reindex_for_setitem(value, self.index)
 
         if is_list_like(value):
             com.require_length_match(value, self.index)
@@ -11923,12 +11918,12 @@ def _from_nested_dict(data) -> collections.defaultdict:
 
 
 def _reindex_for_setitem(
-    value: DataFrame | Series, index: Index, using_cow: bool = False
+    value: DataFrame | Series, index: Index
 ) -> tuple[ArrayLike, BlockValuesRefs | None]:
     # reindex if necessary
 
     if value.index.equals(index) or not len(index):
-        if using_cow and isinstance(value, Series):
+        if using_copy_on_write() and isinstance(value, Series):
             return value._values, value._references
         return value._values.copy(), None