diff --git a/doc/source/whatsnew/v1.5.0.rst b/doc/source/whatsnew/v1.5.0.rst
index 0b450fab53137..62a99ce3cae44 100644
--- a/doc/source/whatsnew/v1.5.0.rst
+++ b/doc/source/whatsnew/v1.5.0.rst
@@ -885,6 +885,7 @@ Indexing
 - Bug when setting a value too large for a :class:`Series` dtype failing to coerce to a common type (:issue:`26049`, :issue:`32878`)
 - Bug in :meth:`loc.__setitem__` treating ``range`` keys as positional instead of label-based (:issue:`45479`)
 - Bug in :meth:`Series.__setitem__` when setting ``boolean`` dtype values containing ``NA`` incorrectly raising instead of casting to ``boolean`` dtype (:issue:`45462`)
+- Bug in :meth:`Series.loc` raising with boolean indexer containing ``NA`` when :class:`Index` did not match (:issue:`46551`)
 - Bug in :meth:`Series.__setitem__` where setting :attr:`NA` into a numeric-dtype :class:`Series` would incorrectly upcast to object-dtype rather than treating the value as ``np.nan`` (:issue:`44199`)
 - Bug in :meth:`DataFrame.loc` when setting values to a column and right hand side is a dictionary (:issue:`47216`)
 - Bug in :meth:`DataFrame.loc` when setting a :class:`DataFrame` not aligning index in some cases (:issue:`47578`)
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 665333d0d7b4f..30d6a8a9f019b 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -30,6 +30,7 @@
 from pandas.core.dtypes.common import (
     is_array_like,
     is_bool_dtype,
+    is_extension_array_dtype,
     is_hashable,
     is_integer,
     is_iterator,
@@ -2531,15 +2532,20 @@ def check_bool_indexer(index: Index, key) -> np.ndarray:
     """
     result = key
     if isinstance(key, ABCSeries) and not key.index.equals(index):
-        result = result.reindex(index)
-        mask = isna(result._values)
-        if mask.any():
+        indexer = result.index.get_indexer_for(index)
+        if -1 in indexer:
             raise IndexingError(
                 "Unalignable boolean Series provided as "
                 "indexer (index of the boolean Series and of "
                 "the indexed object do not match)."
             )
-        return result.astype(bool)._values
+
+        result = result.take(indexer)
+
+        # fall through for boolean
+        if not is_extension_array_dtype(result.dtype):
+            return result.astype(bool)._values
+
     if is_object_dtype(key):
         # key might be object-dtype bool, check_array_indexer needs bool array
         result = np.asarray(result, dtype=bool)
diff --git a/pandas/tests/series/indexing/test_indexing.py b/pandas/tests/series/indexing/test_indexing.py
index 3a8e14576a55d..2f4fffe57593f 100644
--- a/pandas/tests/series/indexing/test_indexing.py
+++ b/pandas/tests/series/indexing/test_indexing.py
@@ -5,7 +5,10 @@
 import numpy as np
 import pytest
 
+from pandas.errors import IndexingError
+
 from pandas import (
+    NA,
     DataFrame,
     IndexSlice,
     MultiIndex,
@@ -330,6 +333,22 @@ def test_loc_setitem_all_false_indexer():
     tm.assert_series_equal(ser, expected)
 
 
+def test_loc_boolean_indexer_non_matching_index():
+    # GH#46551
+    ser = Series([1])
+    result = ser.loc[Series([NA, False], dtype="boolean")]
+    expected = Series([], dtype="int64")
+    tm.assert_series_equal(result, expected)
+
+
+def test_loc_boolean_indexer_miss_matching_index():
+    # GH#46551
+    ser = Series([1])
+    indexer = Series([NA, False], dtype="boolean", index=[1, 2])
+    with pytest.raises(IndexingError, match="Unalignable"):
+        ser.loc[indexer]
+
+
 class TestDeprecatedIndexers:
     @pytest.mark.parametrize("key", [{1}, {1: 1}])
     def test_getitem_dict_and_set_deprecated(self, key):