Copper is an essential trace element and has important role in many metabolic and chemical processes in cells and tissues. Due to their flexible properties, copper-based nanoparticles have been used in many industrial, chemical, electronic and medical applications. As a result of these wide applications exposures of human to these nanoparticles are increased. Oxidative stress and reactive oxygen species (ROS) production are considered the main mechanism by which copper oxide nanoparticles (CUONPs) induce toxicity. Brain is most susceptible to toxicity by CUONPs due to its high content of unsaturated fatty acids and to the relative paucity of antioxidant enzymes in the brain tissue compared with other organs.