<p>Spinal cord ischemia reperfusion injury (SCIRI) induced delayed paraplegia is a complex complication of thoracoabdominal aortic surgery. Reactive oxygen species (ROS) play a critical role in the pathogenesis of delayed paraplegia, suggesting that antioxidants could be a promising therapeutic strategy. Ceria nanomaterials have demonstrated potent antioxidant properties and therapeutic potential in various central nervous system disorders. Herein, the preventive effects of ceria nanoclusters (NCs) against delayed paraplegia were investigated. NCs were synthesized using a facile and green method, incubated with albumin, and exhibited excellent biocompatibility and ROS scavenging activity in vitro, providing neuroprotective effects on neuronal cells. To explore the protective effects against delayed paraplegia in vivo, NCs were intravenously injected into SCIRI rabbits both before ischemia and after reperfusion. Post-reperfusion NCs treatment significantly preserved hindlimb motor function and reduced the incidence of delayed paraplegia. Histopathological and biochemical analyses revealed that NCs protected motor neurons, mitigated oxidative stress, and reduced apoptosis and inflammation in the ischemic spinal cord. These results showed that NCs successfully prevented the development of delayed paraplegia by eliminating excessive ROS.</p><p></p>