diff --git a/Marlin/src/inc/SanityCheck.h b/Marlin/src/inc/SanityCheck.h
index 2d6633b35..97f9a6373 100644
--- a/Marlin/src/inc/SanityCheck.h
+++ b/Marlin/src/inc/SanityCheck.h
@@ -3298,6 +3298,13 @@ static_assert(   _ARR_TEST(3,0) && _ARR_TEST(3,1) && _ARR_TEST(3,2)
   #undef _CLEAN_ASSERT
 #endif
 
+/**
+ * Sanity check for MIXING_EXTRUDER & DISTINCT_E_FACTORS these are not compatible
+ */
+#if ENABLED(MIXING_EXTRUDER) && ENABLED(DISTINCT_E_FACTORS)
+  #error "MIXING_EXTRUDER can't be used with DISTINCT_E_FACTORS. But you may use SINGLENOZZLE with DISTINCT_E_FACTORS."
+#endif
+
 /**
  * Sanity check for valid stepper driver types
  */