Oxidative stress has been implicated in xenobiotic-induced hepatorenal toxicity. This research was designed to investigate the effects of vitamins C and E on tenofovir/nevirapine-induced liver and kidney levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) in male albino rats. Forty five male albino rats were used for this study. The rats were divided into groups A-I of 5 rats each. Group A (placebo control) and group B (solvent control) were orally treated with water and arachis oil respectively. Groups C -F were orally treated with vitamins C, E, combined doses of vitamins C and E, and tenofovir/nevirapine, respectively. Groups G-I were pretreated with vitamins C, E and combined doses of vitamins C and E prior to treatment with tenofovir/nevirapine, respectively. Rats were sacrificed after treatment for 30 days; liver and kidneys were collected and evaluated for the above parameters. Significant (p<0.05) increases in the baseline levels of liver and kidney SOD, GSH, and CAT with decreases in MDA levels were obtained in vitamins C and E treated rats when compared to control. However, treatment with tenofovir/ nevirapine significantly (p<0.05) decreased liver and kidney SOD, GSH, and CAT levels with increases in MDA levels when compared to control. However, all tenofovir/nevirapine -induced alterations were abrogated in rats pretreated vitamins C and E. Abrogation was most pronounced in rats pretreated with combined doses of vitamins C and E. The observations in the present study could be attributed to the inhibitory effects of vitamins C and E on the oxidative activity of tenofovir/nevirapine in the liver and kidneys of treated rats.