Background: El-Wadi and El-Bats drainages considered the main reservoirs for agricultural and domestic non-treated drainage waters at El-Fayoum province. Aims: in the present study is to provide comparable data between El-Wadi, El-Bats drainages and Hawara channel (a branch of the Nile River) with using Nile tilapia (Oreochromis niloticus), as indicator of natural and anthropogenic impacts on aquatic ecosystem. Material and method: Heavy metals evaluated in our work represented in (Fe, Zn, Cd, Cu, and Mn). Moreover, the effect of pollutants and degraded water quality on the biochemical parameters which represented in evaluation of liver functions, kidney functions, protein profile, and lipid profile. . Results : The results showed that The lowest mean value of dissolved oxygen was observed in El-Bats drainage (5.5 mg/l), followed by El-Wadi drainage (5.93 mg/l), this could be attributed to agricultural, industrial, and waste municipal effluents which characterized by high load of organic wastes and the microbial activity that degraded the organic matter led to the oxygen consumption. While the highest mean value of dissolved oxygen (7.98 mg/l) was recorded in Hawara channel (a branch of Nile River). Also, mean value of Cd recorded the lowest concentrations between five heavy metals, and slightly exceeded permissible limit (0.01 ppm), while Zn recorded the highest concentrations in Hawara channel. However, in El-Bats and El-Wadi Drains, Cd showed the lowest concentrations between metals and exceeded permissible limit (0.01 ppm) and Fe showed the highest concentrations that exceeded permissible limit (1 ppm) in great concern according to WHO (1993). The results showed also significant increase of serum Ast, Alt, ALP, LDH activities, and the level of Urea, Uric acid, Creatinine, lipid profile parameters (Triglycerides, Total lipids, and Cholesterol ), and protein profile parameters (Total protein, Albumin, and Globulin ) concentration in Oreochromis niloticus collected from El-Bats and El-Wadi Drains compared with that collected from Hawara channel. From the present results, it can be concluded that deteriorated water quality represented in El-Wadi and El-Bats drainages by highly recorded heavy metals (Fe, Zn, Cd, Cu, and Mn) concentration affect negatively on biochemical parameters of Oreochromis niloticus and vice versa for Oreochromis niloticus collected from Hawara channel (a branch of the Nile River).