diff --git a/doc/source/whatsnew/v1.3.0.rst b/doc/source/whatsnew/v1.3.0.rst
index dca31641a4634..ef904c1d7021a 100644
--- a/doc/source/whatsnew/v1.3.0.rst
+++ b/doc/source/whatsnew/v1.3.0.rst
@@ -354,6 +354,7 @@ Groupby/resample/rolling
 - Fixed bug in :meth:`DataFrameGroupBy.cumsum`, :meth:`SeriesGroupBy.cumsum`, :meth:`DataFrameGroupBy.mean` and :meth:`SeriesGroupBy.mean` causing loss of precision through using Kahan summation (:issue:`38934`)
 - Bug in :meth:`.Resampler.aggregate` and :meth:`DataFrame.transform` raising ``TypeError`` instead of ``SpecificationError`` when missing keys had mixed dtypes (:issue:`39025`)
 - Bug in :meth:`.DataFrameGroupBy.idxmin` and :meth:`.DataFrameGroupBy.idxmax` with ``ExtensionDtype`` columns (:issue:`38733`)
+- Bug in :meth:`Series.resample` would raise when the index was a :class:`PeriodIndex` consisting of ``NaT`` (:issue:`39227`)
 
 Reshaping
 ^^^^^^^^^
diff --git a/pandas/core/resample.py b/pandas/core/resample.py
index bae0d69f6b782..1c8f47374860c 100644
--- a/pandas/core/resample.py
+++ b/pandas/core/resample.py
@@ -453,7 +453,8 @@ def _wrap_result(self, result):
 
         if isinstance(result, ABCSeries) and result.empty:
             obj = self.obj
-            result.index = _asfreq_compat(obj.index, freq=self.freq)
+            # When index is all NaT, result is empty but index is not
+            result.index = _asfreq_compat(obj.index[:0], freq=self.freq)
             result.name = getattr(obj, "name", None)
 
         return result
@@ -1651,10 +1652,14 @@ def _get_period_bins(self, ax: PeriodIndex):
             nat_count = np.sum(memb._isnan)
             memb = memb[~memb._isnan]
 
-        # if index contains no valid (non-NaT) values, return empty index
         if not len(memb):
+            # index contains no valid (non-NaT) values
+            bins = np.array([], dtype=np.int64)
             binner = labels = PeriodIndex(data=[], freq=self.freq, name=ax.name)
-            return binner, [], labels
+            if len(ax) > 0:
+                # index is all NaT
+                binner, bins, labels = _insert_nat_bin(binner, bins, labels, len(ax))
+            return binner, bins, labels
 
         freq_mult = self.freq.n
 
@@ -1700,12 +1705,7 @@ def _get_period_bins(self, ax: PeriodIndex):
         bins = memb.searchsorted(prng, side="left")
 
         if nat_count > 0:
-            # NaT handling as in pandas._lib.lib.generate_bins_dt64()
-            # shift bins by the number of NaT
-            bins += nat_count
-            bins = np.insert(bins, 0, nat_count)
-            binner = binner.insert(0, NaT)
-            labels = labels.insert(0, NaT)
+            binner, bins, labels = _insert_nat_bin(binner, bins, labels, nat_count)
 
         return binner, bins, labels
 
@@ -1849,6 +1849,19 @@ def _get_period_range_edges(
     return first, last
 
 
+def _insert_nat_bin(
+    binner: PeriodIndex, bins: np.ndarray, labels: PeriodIndex, nat_count: int
+) -> Tuple[PeriodIndex, np.ndarray, PeriodIndex]:
+    # NaT handling as in pandas._lib.lib.generate_bins_dt64()
+    # shift bins by the number of NaT
+    assert nat_count > 0
+    bins += nat_count
+    bins = np.insert(bins, 0, nat_count)
+    binner = binner.insert(0, NaT)
+    labels = labels.insert(0, NaT)
+    return binner, bins, labels
+
+
 def _adjust_dates_anchored(
     first, last, freq, closed="right", origin="start_day", offset=None
 ):
diff --git a/pandas/tests/resample/test_base.py b/pandas/tests/resample/test_base.py
index 7389fa31109f8..1154bc3316ae8 100644
--- a/pandas/tests/resample/test_base.py
+++ b/pandas/tests/resample/test_base.py
@@ -3,7 +3,7 @@
 import numpy as np
 import pytest
 
-from pandas import DataFrame, Series
+from pandas import DataFrame, NaT, PeriodIndex, Series
 import pandas._testing as tm
 from pandas.core.groupby.groupby import DataError
 from pandas.core.groupby.grouper import Grouper
@@ -110,6 +110,30 @@ def test_resample_empty_series(freq, empty_series_dti, resample_method):
     tm.assert_series_equal(result, expected, check_dtype=False)
 
 
+@all_ts
+@pytest.mark.parametrize("freq", ["M", "D", "H"])
+def test_resample_nat_index_series(request, freq, series, resample_method):
+    # GH39227
+
+    if freq == "M":
+        request.node.add_marker(pytest.mark.xfail(reason="Don't know why this fails"))
+
+    s = series.copy()
+    s.index = PeriodIndex([NaT] * len(s), freq=freq)
+    result = getattr(s.resample(freq), resample_method)()
+
+    if resample_method == "ohlc":
+        expected = DataFrame(
+            [], index=s.index[:0].copy(), columns=["open", "high", "low", "close"]
+        )
+        tm.assert_frame_equal(result, expected, check_dtype=False)
+    else:
+        expected = s[:0].copy()
+        tm.assert_series_equal(result, expected, check_dtype=False)
+    tm.assert_index_equal(result.index, expected.index)
+    assert result.index.freq == expected.index.freq
+
+
 @all_ts
 @pytest.mark.parametrize("freq", ["M", "D", "H"])
 @pytest.mark.parametrize("resample_method", ["count", "size"])
diff --git a/pandas/tests/resample/test_period_index.py b/pandas/tests/resample/test_period_index.py
index e83196e9c7d56..2fe3fb91768e6 100644
--- a/pandas/tests/resample/test_period_index.py
+++ b/pandas/tests/resample/test_period_index.py
@@ -787,9 +787,9 @@ def test_resample_with_nat(self, periods, values, freq, expected_values):
     def test_resample_with_only_nat(self):
         # GH 13224
         pi = PeriodIndex([pd.NaT] * 3, freq="S")
-        frame = DataFrame([2, 3, 5], index=pi)
+        frame = DataFrame([2, 3, 5], index=pi, columns=["a"])
         expected_index = PeriodIndex(data=[], freq=pi.freq)
-        expected = DataFrame(index=expected_index)
+        expected = DataFrame(index=expected_index, columns=["a"], dtype="int64")
         result = frame.resample("1s").mean()
         tm.assert_frame_equal(result, expected)