diff --git a/doc/source/whatsnew/v2.3.0.rst b/doc/source/whatsnew/v2.3.0.rst
index 09134763977c3..6d813f367374d 100644
--- a/doc/source/whatsnew/v2.3.0.rst
+++ b/doc/source/whatsnew/v2.3.0.rst
@@ -37,6 +37,7 @@ Other enhancements
   updated to work correctly with NumPy >= 2 (:issue:`57739`)
 - :meth:`Series.str.decode` result now has ``StringDtype`` when ``future.infer_string`` is True (:issue:`60709`)
 - :meth:`~Series.to_hdf` and :meth:`~DataFrame.to_hdf` now round-trip with ``StringDtype``  (:issue:`60663`)
+- The :meth:`DataFrame.iloc` now works correctly with ``copy_on_write`` option when assigning values after subsetting the columns of a DataFrame and using a slice (:issue:`60309`)
 - The :meth:`Series.str.decode` has gained the argument ``dtype`` to control the dtype of the result (:issue:`60940`)
 - The :meth:`~Series.cumsum`, :meth:`~Series.cummin`, and :meth:`~Series.cummax` reductions are now implemented for ``StringDtype`` columns (:issue:`60633`)
 - The :meth:`~Series.sum` reduction is now implemented for ``StringDtype`` columns (:issue:`59853`)
diff --git a/pandas/core/internals/managers.py b/pandas/core/internals/managers.py
index a3738bb25f56c..2e6701916a8d4 100644
--- a/pandas/core/internals/managers.py
+++ b/pandas/core/internals/managers.py
@@ -572,7 +572,12 @@ def setitem(self, indexer, value) -> Self:
                         0, blk_loc, values
                     )
                     # first block equals values
-                    self.blocks[0].setitem((indexer[0], np.arange(len(blk_loc))), value)
+                    col_indexer: slice | np.ndarray
+                    if isinstance(indexer[1], slice) and indexer[1] == slice(None):
+                        col_indexer = slice(None)
+                    else:
+                        col_indexer = np.arange(len(blk_loc))
+                    self.blocks[0].setitem((indexer[0], col_indexer), value)
                     return self
             # No need to split if we either set all columns or on a single block
             # manager
diff --git a/pandas/tests/indexing/test_iloc.py b/pandas/tests/indexing/test_iloc.py
index 2f6998a85c80b..d38169c76d584 100644
--- a/pandas/tests/indexing/test_iloc.py
+++ b/pandas/tests/indexing/test_iloc.py
@@ -22,6 +22,7 @@
     date_range,
     interval_range,
     isna,
+    option_context,
     to_datetime,
 )
 import pandas._testing as tm
@@ -1448,3 +1449,26 @@ def test_iloc_nullable_int64_size_1_nan(self):
         result = DataFrame({"a": ["test"], "b": [np.nan]})
         with pytest.raises(TypeError, match="Invalid value"):
             result.loc[:, "b"] = result.loc[:, "b"].astype("Int64")
+
+    def test_iloc_setitem_list_with_cow(self):
+        # GH#60309
+        with option_context("mode.copy_on_write", True):
+            dftest = DataFrame(
+                {"A": [1, 4, 1, 5], "B": [2, 5, 2, 6], "C": [3, 6, 1, 7]}
+            )
+            df = dftest[["B", "C"]]
+
+            # Perform the iloc operation
+            df.iloc[[1, 3], :] = [[2, 2], [2, 2]]
+
+            # Check that original DataFrame is unchanged
+            expected_orig = DataFrame(
+                {"A": [1, 4, 1, 5], "B": [2, 5, 2, 6], "C": [3, 6, 1, 7]}
+            )
+            tm.assert_frame_equal(dftest, expected_orig)
+
+            # Check that df is modified correctly
+            expected_df = DataFrame(
+                {"B": [2, 2, 2, 2], "C": [3, 2, 1, 2]}, index=df.index
+            )
+            tm.assert_frame_equal(df, expected_df)