diff --git a/django/db/models/constraints.py b/django/db/models/constraints.py
index 49c7c91de9..c2c7bb06f6 100644
--- a/django/db/models/constraints.py
+++ b/django/db/models/constraints.py
@@ -2,7 +2,7 @@ from enum import Enum
 
 from django.core.exceptions import FieldError, ValidationError
 from django.db import connections
-from django.db.models.expressions import Exists, ExpressionList, F
+from django.db.models.expressions import Exists, ExpressionList, F, OrderBy
 from django.db.models.indexes import IndexExpression
 from django.db.models.lookups import Exact
 from django.db.models.query_utils import Q
@@ -338,10 +338,12 @@ class UniqueConstraint(BaseConstraint):
                     meta=model._meta, exclude=exclude
                 ).items()
             }
-            expressions = [
-                Exact(expr, expr.replace_expressions(replacements))
-                for expr in self.expressions
-            ]
+            expressions = []
+            for expr in self.expressions:
+                # Ignore ordering.
+                if isinstance(expr, OrderBy):
+                    expr = expr.expression
+                expressions.append(Exact(expr, expr.replace_expressions(replacements)))
             queryset = queryset.filter(*expressions)
         model_class_pk = instance._get_pk_val(model._meta)
         if not instance._state.adding and model_class_pk is not None:
diff --git a/docs/releases/4.1.6.txt b/docs/releases/4.1.6.txt
index a581572a9a..e97c25aea0 100644
--- a/docs/releases/4.1.6.txt
+++ b/docs/releases/4.1.6.txt
@@ -10,4 +10,5 @@ in 4.1.5.
 Bugfixes
 ========
 
-* ...
+* Fixed a bug in Django 4.1 that caused a crash of model validation on
+  ``UniqueConstraint`` with ordered expressions (:ticket:`34291`).
diff --git a/tests/constraints/tests.py b/tests/constraints/tests.py
index 5a498f0d73..223b4b3cd5 100644
--- a/tests/constraints/tests.py
+++ b/tests/constraints/tests.py
@@ -672,6 +672,29 @@ class UniqueConstraintTests(TestCase):
             exclude={"name"},
         )
 
+    def test_validate_ordered_expression(self):
+        constraint = models.UniqueConstraint(
+            Lower("name").desc(), name="name_lower_uniq_desc"
+        )
+        msg = "Constraint “name_lower_uniq_desc” is violated."
+        with self.assertRaisesMessage(ValidationError, msg):
+            constraint.validate(
+                UniqueConstraintProduct,
+                UniqueConstraintProduct(name=self.p1.name.upper()),
+            )
+        constraint.validate(
+            UniqueConstraintProduct,
+            UniqueConstraintProduct(name="another-name"),
+        )
+        # Existing instances have their existing row excluded.
+        constraint.validate(UniqueConstraintProduct, self.p1)
+        # Unique field is excluded.
+        constraint.validate(
+            UniqueConstraintProduct,
+            UniqueConstraintProduct(name=self.p1.name.upper()),
+            exclude={"name"},
+        )
+
     def test_validate_expression_condition(self):
         constraint = models.UniqueConstraint(
             Lower("name"),