Fluoride is one of the common environmental pollutants. Its excessive exposure results in a wide array of toxicity phenotypes including oxidative stress, skeletal and soft tissue damage etc. Antioxidants such as Selenium (Se) and α-tocopherol are attractive agents for oxidative stress prevention because of their safety profile and wide availability. It is known that in combination, Se and alpha-tocopherol act synergistically against ROS formation. This study investigated the protective effects of selenium (05 µg/kg BW) and Alpha-tocopherol (2 mg/kg BW) on markers of oxidative stress in brain and muscle of mice exposed to sodium fluoride (20mg/kg BW) for 15 days. The results showed significant (p<0.05) alterations in markers of oxidative stress includes; an increase in xanthine oxidase activity and lipid peroxidation, a decline in SOD, CAT, GST and GPx activities in fluoride exposure group in comparison with control group indicates oxidative stress induced by fluoride. These changes were reversed modestly in Se and alpha-tocopherol alone treated groups and significantly  (p<0.05) in the combinedly treated group indicating synergistic action in mitigation of fluoride effect.