diff --git a/Misc/NEWS b/Misc/NEWS
index e9a370c9788..c57b165ccd6 100644
--- a/Misc/NEWS
+++ b/Misc/NEWS
@@ -316,6 +316,9 @@ Tests
 Build
 -----
 
+- Fix cross compiling issue in setup.py, ensure that lib_dirs and inc_dirs are
+  defined in cross compiling mode, too.
+
 - Issue #16593: Have BSD 'make -s' do the right thing, thanks to Daniel Shahaf
 
 - Issue #16262: fix out-of-src-tree builds, if mercurial is not installed.
diff --git a/setup.py b/setup.py
index 8a9ba5f4276..8125efcb4e6 100644
--- a/setup.py
+++ b/setup.py
@@ -506,6 +506,9 @@ class PyBuildExt(build_ext):
                 '/lib', '/usr/lib',
                 ]
             inc_dirs = self.compiler.include_dirs + ['/usr/include']
+        else:
+            lib_dirs = []
+            inc_dirs = []
         exts = []
         missing = []