Organic pollution is one of the environmental hazards, especially in aquatic ecosystems. This study was focusing on levels of total organic carbon (TOC%) in the sediment of two freshwater habitats different in quality, as well as tissues including; muscles and gonads of two fish species inhabiting both sites during four seasons of one year of study. Ammar drain as a polluted site showed significantly higher levels of TOC% in both sediment and fish tissues comparing to River Nile as a reference site. Data also illustrated that fish from the polluted site showed a remarkable decrease in blood indices; RBCs count, Hb content, and Hct%, while WBCs count was mostly elevated, especially during autumn. Accompanying these results, antioxidant enzymes as superoxide dismutase (SOD) and catalase (CAT) were generally decreased during most seasons in fish samples from Ammar drain. Also, histopathological changes in muscles and gonads were observed, where to severe deteriorations in these tissues were more discriminating in fish species from Ammar drain compared to River Nile locality. From the obtained results, polluted water drains affect the general health and structure of their inhabiting fish species.