This work is concerned with studying the effect of various pollutants in Lake Manzala on fish quality by investigating the biochemical characteristics of Nile tilapia fish collected during the winter and summer seasons in 2020. The biochemical parameters of Nile tilapia fish were significantly different between the two seasons at all investigated stations. However, blood creatinine, urea, and uric acid showed the highest levels in fish collected from Bahr El-Baqer and El-Matariya during the study. Fish from polluted stations recorded an increase in serum cholesterol levels in the cold season, and triglycerides levels of O. niloticus showed remarkable variations. Alterations in the physiological blood parameters reflect changes in the organism's metabolic and biochemical factors as a result of the effects of various pollutants, and they allow researchers to evaluate the mechanisms of pollutants' impacts.