Spinal cord injury (SCI) is one of the most devastating diseases that may cause paralysis, disability and irreversible loss of functions, which ultimately lead to permanent disabilities and a decrease in patient life expectancy. Coenzyme Q10 (CoQ10) is a lipid-soluble vitamin-like benzoquinone compound that can exert antioxidant and anti-apoptotic functions in a variety of diseases. However, the antioxidant and anti-apoptotic effects of CoQ10 in the treatment of SCI are still unknown. Therefore, we designed experiments to measure the changes in antioxidant capacity (glutathione (GSH), superoxide dismutase (SOD) and the end product of lipid peroxidation (MDA)) and apoptosis products (Bax, Bcl-2 and Caspase-3) to evaluate the protective effects of CoQ10 on SCI and investigated whether CoQ10 exerts its functions through the Nrf-2/NQO-1 and NF-kappa B signaling pathway. Our results showed that CoQ10 treatment could significantly decrease the levels of oxidative products (MDA) and increase the activities of antioxidant enzymes (SOD and GSH) against oxidative stress, as well as decrease the levels of pro-apoptotic proteins (Bax and Caspase-3) and increase the levels of anti-apoptotic proteins (Bcl-2) against apoptosis after SCI. We also observed that CoQ10 exerted beneficial effects through the Nrf-2/NQO-1 and NF-kappa B signaling pathway. These findings suggested that CoQ10 had a protective effect by decreasing oxidative stress and apoptosis after SCI. Thus, our data may provide a new approach wherein CoQ10 may be considered as a potential effective therapeutic for the treatment of SCI.