There is increasing scientific evidences that the physical and chemical properties of manufactured nanoparticles lead to an increase in their bioavailability and toxicity. Among them Copper oxide nanoparticles (CuO-NPs) are widely used in different fields. However their potential adverse effects namely on brain functions are still discussed. Thus, the present study aimed to investigate the subacute oral toxicity and effects of CuO-NPs on cognitive performances in rats. Rats were randomly divided into three groups of 8 animals each, a control group received a dose 9‰ sodium chloride and the other groups received a suspension of CuO-NPs at doses of 250 and 500 mg/kg through oral gavage for 14 consecutive days. Multiple behavioral tests showed that CuO-NPs caused little changes in memory and learning performances as well as the locomotors activity, while the anxiety index increased. Copper NPs exposure increased also the liver and stomach relative weights and altered some blood biochemical parameters.