diff --git a/libc/CMakeLists.txt b/libc/CMakeLists.txt
--- a/libc/CMakeLists.txt
+++ b/libc/CMakeLists.txt
@@ -71,9 +71,13 @@
   message(STATUS "Set COMPILER_RESOURCE_DIR to "
                  "${COMPILER_RESOURCE_DIR} using --print-resource-dir")
 else()
-  set(COMPILER_RESOURCE_DIR OFF)
-  message(STATUS "COMPILER_RESOURCE_DIR not set
-                  --print-resource-dir not supported by host compiler")
+  if (LIBC_TARGET_ARCHITECTURE_IS_GPU)
+    message(FATAL_ERROR "COMPILER_RESOURCE_DIR must be set for GPU builds")
+  else()
+    set(COMPILER_RESOURCE_DIR OFF)
+    message(STATUS "COMPILER_RESOURCE_DIR not set
+                    --print-resource-dir not supported by host compiler")
+  endif()
 endif()
 
 option(LLVM_LIBC_FULL_BUILD "Build and test LLVM libc as if it is the full libc" OFF)
diff --git a/libc/cmake/modules/LLVMLibCObjectRules.cmake b/libc/cmake/modules/LLVMLibCObjectRules.cmake
--- a/libc/cmake/modules/LLVMLibCObjectRules.cmake
+++ b/libc/cmake/modules/LLVMLibCObjectRules.cmake
@@ -68,6 +68,11 @@
   if (LIBC_TARGET_ARCHITECTURE_IS_GPU)
     list(APPEND compile_options "-nogpulib")
     list(APPEND compile_options "-fvisibility=hidden")
+
+    # Manually disable all standard include paths and include the resource
+    # directory to prevent system headers from being included.
+    list(APPEND compile_options "-isystem${COMPILER_RESOURCE_DIR}/include")
+    list(APPEND compile_options "-nostdinc")
   endif()
   set(${output_var} ${compile_options} PARENT_SCOPE)
 endfunction()