Today, due to technology development and aversive events of daily life, Human exposure to both radiofrequency and stress is unavoidable. This study investigated the co-exposure to repeated restraint stress and WiFi signal on cognitive function and oxidative stress in brain of male rats. Animals were divided into four groups: Control, WiFi-exposed, restrained and both WiFi-exposed and restrained groups. Each of WiFi exposure and restraint stress occurred 2 h (h)/day during 20 days. Subsequently, various tests were carried out for each group, such as anxiety in elevated plus maze, spatial learning abilities in the water maze, cerebral oxidative stress response and cholinesterase activity in brain and serum. Results showed that WiFi exposure and restraint stress, alone and especially if combined, induced an anxiety-like behavior without impairing spatial learning and memory abilities in rats. At cerebral level, we found an oxidative stress response triggered by WiFi and restraint, per se and especially when combined as well as WiFi-induced increase in acetylcholinesterase activity. Our results reveal that there is an impact of WiFi signal and restraint stress on the brain and cognitive processes especially in elevated plus maze task. In contrast, there are no synergistic effects between WiFi signal and restraint stress on the brain.