Copper is an integral part of many important enzymes involved in a number of vital biological processes. Even though it is essential to life, at elevated tissue concentrations, copper can become toxic to cells. Recent studies have reported oxidative damage due to copper in various tissues. Considering the vulnerability of the brain to oxidative stress, this study was undertaken to explore possible beneficial antioxidant effects of N-acetylcysteine on oxidative stress induced by copper overload in brain tissue of rats. Thirty-two Wistar rats were equally divided into four groups. The first group was used as control. The second, third, and fourth groups were given 1 g/L copper in their drinking water for 1 month. At the end of this period, the group 2 rats were sacrificed. During the next 2 weeks, the rats in group 3 were injected intraperitoneally with physiological saline and those in group 4 with 20 mg/kg intraperitoneal injections of N-acetylcysteine. In group 2 the lipid peroxidation and nitric oxide levels were increased in the brain cortex while the activities of superoxide dismutase and catalase and the concentration of glutathione were decreased. In rats treated with N-acetylcysteine, lipid peroxidation decreased and the activities of antioxidant enzyme improved in the brain cortex. In conclusion, treatment with N-acetylcysteine modulated the antioxidant redox system and reduced brain oxidative stress induced by copper.