Selenium and vitamin E are very effective antioxidant agents which play important roles in improving and development of aquaculture sector. This study was conducted to determine the protective and treatment effects of vitamin E and selenium against lead toxicity. Administration of both vitamin E and selenium ameliorated the adverse effects of lead acetate toxicity through significant increase in hemoglobin, packed cell volume, RBC count, WBC count, and lymphocytes compared to lead acetate-exposed groups especially after the 10th week. Also, it is revealed that severe decrease of total protein, calcium, phosphorous, and magnesium in lead acetate intoxicated group. On contrary, significant increase of blood parameters upon addition of vitamin E and selenium combined with/without lead. On the other hand, insignificant decreases of sAST, sALT, urea, and creatinine in group fed on vitamin E and selenium, while increase in lead acetate intoxicated group. Lead acetate caused increasing of lipid peroxidation level (malondialdehyde) and decreasing of superoxide dismutase activity and reduced glutathione level. From these results, it is concluded that exposure to lead acetate is considered as hepatotoxic environmental pollutant. Exposure to lead acetate induced significant effects on antioxidant status. Antioxidants (vitamin E and selenium) showed important roles to protect body against lipid peroxidation, which considered as the first step of cell membrane damage, in addition to the improvement of the endogenous antioxidant enzyme activities.