diff --git a/doc/source/whatsnew/v2.1.1.rst b/doc/source/whatsnew/v2.1.1.rst
index e7bfda82494a3..d0882bdf094ad 100644
--- a/doc/source/whatsnew/v2.1.1.rst
+++ b/doc/source/whatsnew/v2.1.1.rst
@@ -15,6 +15,7 @@ Fixed regressions
 ~~~~~~~~~~~~~~~~~
 - Fixed regression in :func:`merge` when merging over a PyArrow string index (:issue:`54894`)
 - Fixed regression in :func:`read_csv` when ``usecols`` is given and ``dtypes`` is a dict for ``engine="python"`` (:issue:`54868`)
+- Fixed regression in :func:`read_csv` when ``delim_whitespace`` is True (:issue:`54918`, :issue:`54931`)
 - Fixed regression in :meth:`.GroupBy.get_group` raising for ``axis=1`` (:issue:`54858`)
 - Fixed regression in :meth:`DataFrame.__setitem__` raising ``AssertionError`` when setting a :class:`Series` with a partial :class:`MultiIndex` (:issue:`54875`)
 - Fixed regression in :meth:`Series.drop_duplicates` for PyArrow strings (:issue:`54904`)
diff --git a/pandas/_libs/src/parser/tokenizer.c b/pandas/_libs/src/parser/tokenizer.c
index abd3fb9e1fef3..ce8a38df172ef 100644
--- a/pandas/_libs/src/parser/tokenizer.c
+++ b/pandas/_libs/src/parser/tokenizer.c
@@ -664,7 +664,8 @@ static int parser_buffer_bytes(parser_t *self, size_t nbytes,
     ((!self->delim_whitespace && c == ' ' && self->skipinitialspace))
 
 // applied when in a field
-#define IS_DELIMITER(c) ((c == delimiter) || (delim_whitespace && isblank(c)))
+#define IS_DELIMITER(c) \
+    ((!delim_whitespace && c == delimiter) || (delim_whitespace && isblank(c)))
 
 #define _TOKEN_CLEANUP()                                                \
     self->stream_len = slen;                                            \
diff --git a/pandas/tests/io/parser/test_header.py b/pandas/tests/io/parser/test_header.py
index 5cb54bb4e2916..d72174c40478e 100644
--- a/pandas/tests/io/parser/test_header.py
+++ b/pandas/tests/io/parser/test_header.py
@@ -658,3 +658,29 @@ def test_header_missing_rows(all_parsers):
     msg = r"Passed header=\[0,1,2\], len of 3, but only 2 lines in file"
     with pytest.raises(ValueError, match=msg):
         parser.read_csv(StringIO(data), header=[0, 1, 2])
+
+
+@skip_pyarrow
+def test_header_multiple_whitespaces(all_parsers):
+    # GH#54931
+    parser = all_parsers
+    data = """aa    bb(1,1)   cc(1,1)
+                0  2  3.5"""
+
+    result = parser.read_csv(StringIO(data), sep=r"\s+")
+    expected = DataFrame({"aa": [0], "bb(1,1)": 2, "cc(1,1)": 3.5})
+    tm.assert_frame_equal(result, expected)
+
+
+@skip_pyarrow
+def test_header_delim_whitespace(all_parsers):
+    # GH#54918
+    parser = all_parsers
+    data = """a,b
+1,2
+3,4
+    """
+
+    result = parser.read_csv(StringIO(data), delim_whitespace=True)
+    expected = DataFrame({"a,b": ["1,2", "3,4"]})
+    tm.assert_frame_equal(result, expected)