Background: Energy drinks (EDs) became a worldwide phenomenon and popular especially among young adult and the brain is one of the most vulnerable organs to toxicity. Objective: This work aimed to study the sub chronic effect of consumption of two different popular energy drinks (power horse and red bull) on the brain of adult male albino rats through biochemical, histological and cytogenetic parameters, and to determine the possible protective role of Omega-3 on the adverse effects of EDs. Also, to determine the effects of EDs withdrawal (recovery period). Methodology: Forty-eight adult male albino rats were divided into 8 groups; control, omega 3, RB, PH, each of EDs combined with omega 3 and after 2 weeks of withdrawal. Blood samples, brains and femora from the rats were obtained for biochemical, histological and cytogenetic evaluation. Results: The studied EDs resulted in elevation of the oxidative stress marker malondialdehyde, structural and numerical chromosomal aberrations. While they decreased the antioxidant markers (catalase and Superoxide dismutase), acetylcholinesterase activity, total content of DNA and RNA in brain tissue and the mitotic index with disturbance in the normal histology of the brain. Either treatment with omega 3 or EDs withdrawal improve these changes with better effect to omega 3. Conclusion: EDs are toxic to the brain. Omega 3 or EDs withdrawal can ameliorate this toxicity with better effect to omega 3. Therefore, strict control of EDs consumption is urgently needed.