Utilizing immunocompromised SCID mice after spinal cordinjury (SCI), we performed motor function, electrophysiology,histochemistry analyses and demonstrated that SCID micedisplayed improved CNS functional recovery compared toWT mice after SCI, while SCID mice without injury performedworse in Morris water maze test. Unbiased RNA-sequencinganalysis of spinal cord transcriptomes revealed that SCIDmice had reduced expression of immune function-relatedgenes and heightened expression of neural transmissionrelated genes both before and after SCI, indicating that notonly reduced inflammation after injury but also dampenedsteady-state immune function without injury heightened theneurotransmission program, resulting in better or worsebehavioral outcomes respectively, under pathological orphysiological conditions. This study revealed an interestingand intricate relationship between immune and neuralfunctions.