Abstract: Background and Objective: Young and adolescents ingest the caffeinated energy drinks (ED) to enhance their mental and physical performances and improve alertness and concentration alone or by mixing them with other stimulants such as Catha edulis leaves. This study aimed to investigate the effect of mixing caffeine and Catha edulis on the antioxidants of brain cortices of rabbits. Materials and Methods: Three groups of rabbits received Catha edulis and caffeine for 35 days at doses of 5 mL kg–1 and 1.1 mg, respectively, alone or together. The fourth group served as control. At the end of the study rabbits brain cortices were removed and different antioxidant and histopathological tests were performed. Results: Reduced activity of catalase and thiol contents were observed following exposure to caffeine and/or Catha edulis with changing in the levels of protein, albumin, glucose, cholesterol urea and UA as compared to control group. Conclusion: It is concluded that consumption of caffeinated ED and/or Catha edulis are responsible of biochemical changes as well as histopathology of the brain cortices of rabbits.