The primary objective of this study was to determine the possible apoptotic cell death preventive effects of the antioxidant selenium using an experimental rat spinal cord injury (SCI) model and cultured spinal cord-derived neural progenitor cells (NPCs). Sodium selenite treatment exerted a profound preventive effect on apoptotic cell death, including p-P38, p-SAPK/JNK, caspases, and PARP activity, and ameliorated astrogliosis and hypomyelination, which occurs in regions of active cell death in the spinal cords of SCI rats. The foremost protective effect of selenite in SCI would therefore be manifested in the suppression of acute secondary apoptotic cell death. However, selenite does not appear to exert an anti-inflammatory function associated with active microglia and macrophage propagation or infiltration into the lesion site. Selenite-mediated neuroprotection has been linked to selenite's attenuation or inhibition of p38 mitogen-activated protein kinase, pSAPK/JNK, and Bax activation in in vitro and in vivo SCI lesion sites. Selenite also attenuated cell death via the prevention of cytochrome c release, caspase activation, and ROS accumulation in the cytosol. Also, our study showed that selenite administered immediately after SCI significantly diminishes functional deficits. The selenite-treated group recovered hind limb reflexes more rapidly, and a higher percentage of these rats regained responses to a greater degree than was seen in the untreated injured rats. Our data indicate that the therapeutic outcome of selenite is most likely the consequence of its comprehensive apoptotic cell death blocking effects, resulting in the protection of white matter, oligodendrocytes, and neurons, and the inhibition of astrogliosis. The finding that the administration of selenite prevents secondary pathological events in traumatic spinal cord injuries, and promotes the recovery of motor function in an animal model. Its efficacy may facilitate the development of novel drug targets for the treatment of SCI.