Background The neuroprotective effects of xenon post-conditioning following spinal cord injury remain unknown. We monitored the effect of xenon post-conditioning on the spinal cord following ischaemia-reperfusion injury and determined its mechanism of action. Methods Spinal cord ischaemia was induced following balloon occlusion of the thoracic aorta in male Sprague-Dawley rats. Rats were divided into three groups (n?=?30 in each group). The control group underwent ischaemia-reperfusion injury and immediately inhaled 50% (v/v) nitrogen at the time of reperfusion for 60?min continuously. The xenon-post-conditioning group underwent the same surgical procedure and immediately inhaled 50% (v/v) xenon at the time of reperfusion for 60?min continuously. The sham operation group underwent the same surgical procedure without aortic catheter occlusion and inhaled the same gas as that in control rats. Neurologic function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48?h after reperfusion. Histological changes were observed using Nissl staining, the ultrastructure of the spinal cord was examined using transmission electron microscopy, and apoptosis was monitored using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling. Results Compared with the control group, the xenon-post-conditioning group showed improved neurologic outcomes (11.3?+/-?1.6 vs. 15.7?+/-?3.1, respectively) and had more morphologically normal neurons (6?+/-?2 vs. 12?+/-?3) at 48?h after reperfusion. Moreover, apoptotic cell death in xenon-treated rats was reduced when compared with control rats (18.29?+/-?3.06 vs. 27.34?+/-?3.63, P?<?0.05, respectively). Conclusions Xenon post-conditioning exerts a neuroprotective effect on the spinal cord following ischaemia-reperfusion injury via its anti-apoptotic role.