diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index a07226ef0f50a..f73fe77defc26 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -6865,12 +6865,15 @@ def get_slice_bound(self, label, side: Literal["left", "right"]) -> int:
         # we need to look up the label
         try:
             slc = self.get_loc(label)
-        except KeyError as err:
+        except KeyError:
             try:
                 return self._searchsorted_monotonic(label, side)
             except ValueError:
-                # raise the original KeyError
-                raise err from None
+                raise KeyError(
+                    f"Cannot get {side} slice bound for non-monotonic index "
+                    f"with a missing label {original_label!r}. "
+                    "Either sort the index or specify an existing label."
+                ) from None
 
         if isinstance(slc, np.ndarray):
             # get_loc may return a boolean array, which
diff --git a/pandas/tests/frame/indexing/test_indexing.py b/pandas/tests/frame/indexing/test_indexing.py
index d11c2ef8a3a3c..2293ca375be70 100644
--- a/pandas/tests/frame/indexing/test_indexing.py
+++ b/pandas/tests/frame/indexing/test_indexing.py
@@ -564,9 +564,10 @@ def test_getitem_setitem_integer_slice_keyerrors(self):
 
         # non-monotonic, raise KeyError
         df2 = df.iloc[list(range(5)) + list(range(5, 10))[::-1]]
-        with pytest.raises(KeyError, match=r"^3$"):
+        msg = "non-monotonic index with a missing label 3"
+        with pytest.raises(KeyError, match=msg):
             df2.loc[3:11]
-        with pytest.raises(KeyError, match=r"^3$"):
+        with pytest.raises(KeyError, match=msg):
             df2.loc[3:11] = 0
 
     def test_fancy_getitem_slice_mixed(self, float_frame, float_string_frame):
diff --git a/pandas/tests/indexes/numeric/test_indexing.py b/pandas/tests/indexes/numeric/test_indexing.py
index 2f37b15ca74f5..0a88f55b06af8 100644
--- a/pandas/tests/indexes/numeric/test_indexing.py
+++ b/pandas/tests/indexes/numeric/test_indexing.py
@@ -600,10 +600,11 @@ def test_slice_locs_na(self):
 
     def test_slice_locs_na_raises(self):
         index = Index([np.nan, 1, 2])
-        with pytest.raises(KeyError, match="1.5"):
+        msg = "non-monotonic index with a missing label 1.5"
+        with pytest.raises(KeyError, match=msg):
             index.slice_locs(start=1.5)
 
-        with pytest.raises(KeyError, match="1.5"):
+        with pytest.raises(KeyError, match=msg):
             index.slice_locs(end=1.5)
 
 
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 91111d0b1b0ea..372120362b5d6 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -3162,9 +3162,10 @@ def test_loc_getitem_setitem_integer_slice_keyerrors(self):
 
         # non-monotonic, raise KeyError
         s2 = ser.iloc[list(range(5)) + list(range(9, 4, -1))]
-        with pytest.raises(KeyError, match=r"^3$"):
+        msg = "non-monotonic index with a missing label 3"
+        with pytest.raises(KeyError, match=msg):
             s2.loc[3:11]
-        with pytest.raises(KeyError, match=r"^3$"):
+        with pytest.raises(KeyError, match=msg):
             s2.loc[3:11] = 0
 
     def test_loc_getitem_iterator(self, string_series):
diff --git a/pandas/tests/series/indexing/test_indexing.py b/pandas/tests/series/indexing/test_indexing.py
index 32ca3f1ba11c3..bffdae5977c23 100644
--- a/pandas/tests/series/indexing/test_indexing.py
+++ b/pandas/tests/series/indexing/test_indexing.py
@@ -404,6 +404,13 @@ def test_setitem_empty_indexer(indexer, val):
     tm.assert_frame_equal(df, expected)
 
 
+def test_loc_non_monotonic_index_with_a_missing_label():
+    msg = "Cannot get left slice bound for non-monotonic index with a missing label 4"
+    ser = Series([3, 6, 7, 6], index=[3, 8, 7, 6])
+    with pytest.raises(KeyError, match=msg):
+        ser.loc[4:7]
+
+
 class TestDeprecatedIndexers:
     @pytest.mark.parametrize("key", [{1}, {1: 1}])
     def test_getitem_dict_and_set_deprecated(self, key):