diff --git a/pandas/core/arrays/datetimelike.py b/pandas/core/arrays/datetimelike.py
index bb21bed2dc779..816d8abec1428 100644
--- a/pandas/core/arrays/datetimelike.py
+++ b/pandas/core/arrays/datetimelike.py
@@ -1897,7 +1897,12 @@ def _validate_frequency(cls, index, freq, **kwargs):
 
         try:
             on_freq = cls._generate_range(
-                start=index[0], end=None, periods=len(index), freq=freq, **kwargs
+                start=index[0],
+                end=None,
+                periods=len(index),
+                freq=freq,
+                unit=index.unit,
+                **kwargs,
             )
             if not np.array_equal(index.asi8, on_freq.asi8):
                 raise ValueError
diff --git a/pandas/tests/frame/methods/test_asfreq.py b/pandas/tests/frame/methods/test_asfreq.py
index 5b3e1614e1ada..9fa9f27e7e312 100644
--- a/pandas/tests/frame/methods/test_asfreq.py
+++ b/pandas/tests/frame/methods/test_asfreq.py
@@ -17,6 +17,10 @@
 
 
 class TestAsFreq:
+    @pytest.fixture(params=["s", "ms", "us", "ns"])
+    def unit(self, request):
+        return request.param
+
     def test_asfreq2(self, frame_or_series):
         ts = frame_or_series(
             [0.0, 1.0, 2.0],
@@ -197,3 +201,11 @@ def test_asfreq_with_unsorted_index(self, frame_or_series):
 
         result = result.asfreq("D")
         tm.assert_equal(result, expected)
+
+    def test_asfreq_after_normalize(self, unit):
+        # https://github.com/pandas-dev/pandas/issues/50727
+        result = DatetimeIndex(
+            date_range("2000", periods=2).as_unit(unit).normalize(), freq="D"
+        )
+        expected = DatetimeIndex(["2000-01-01", "2000-01-02"], freq="D").as_unit(unit)
+        tm.assert_index_equal(result, expected)