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Lake Qarun is exposed to high inputs of agricultural drainage water, sewage and industrial wastewater through a system of twelve drains which influence the living organisms like fish.Water and fish samples were collected from Lake Qarun seasonally during (August 2014 to May 2015) to determine physicochemical parameters and heavy metals concentrations in water as well as accumulated levels of heavy metals in fish tissues (liver, muscle and gill) of (T. ziliii and M. capito) fish of the lake. In addition, the study determined the changes in the activities of antioxidant defense enzymes, liver enzymes and performing meat quality. The results showed that Al-Batts and Al-Wadi Drains contained the highest amount of ammonia, nitrite and nitrate. Pollutants decreased as the distance from two drains and two pump stations increased, which seemed that sampling sites (B1, W1, P1 and K1) are the main source of pollution and more polluted than other sampling points. The activities of antioxidant defense enzymes (superoxide dismutase and catalase) exhibited an increase in the liver of fish in the lake. On contrary, liver enzymes (ALT, AST, and ALP) were decreased significantly (p 05).