This study was initiated to evaluate the effect of hazardous exposure to water pollutants on Tilapia zilli Gerv inhabiting Lake Maryût at 3 different sites with varying degrees of physicochemical and organic criteria. As compared to other sites, the lower water turbidity and alkalinity plus lesser metal content in site #1, signify its picking as reference.The expected anoxicity of the polluted sites (#2& #3) was evidenced by the elevated chemicaland biological-oxygen demands added to reduced dissolved oxygen. Abundant phytoplankton and sewage effluents coupled with the high productivity of the lake have elevated water pH and nutrient salts; thus causing a chronic eutrophication problem. Emerging evidence suggests that T. zilli responded differently according to the environmental stress index in each catch area. In polluted fish, serum hyper-αl-, α 2 -, and β-globulinemia plus low albumin added to the enhanced activities of serum transaminases and lactate dehydrogenase suggests chronic functional damage in the liver. However, the hyper-y-globulinemia implies an indirect challenge response toward the invasion of endoand ectoparasites. Serum enzymes, protein, lipid, cholesterol, creatinine, and glucose fluctuated in a positive correlation contra the guidelines of water pollutants; they are thus validated as beneficial "biochemical markers" for contamination stress. Unlike other biological principles investigated, alkaline phosphatase proved to be a promising "model" for appraising moderate, sublethal, or metal-restricted contamination. Other water pollutants, as petroleum oil, seem to interfere with this peculiarity.