Abstract: Background and Objective: Fish health and aquatic environment are strongly interrelated. Aquatic environment receive array of anthropogenically derived chemicals with deleterious health effects on the cohabitant aquatic animals and threatens their lives. The aim of this study was to evaluate the health status of Tilapia zillii and Solea vulgaris captured from Lake Qarun, Egypt known to receive lofty loads of contaminants as well as to monitor the genotoxic effects of some heavy metals detected in lake water on the two fish species. Methodology: Heavy metals (Cu, Zn, Cd, Ni and Pb) were assessed in water and fish specimens (Tilapia zillii and Solea vulgaris) collected from Lake Qarun and the mean value was recorded. Fish and water samples were subjected to microbiological and parasitological examination. Additionally, genotoxicity was analysed using comet assay. Results: Heavy metals; Zn, Ni and Cu showed high values in water exceeding the recommended limits. Accumulation of heavy metals was noticed in fish muscles and Ni was the uppermost detected metal. Genotoxicity was confirmed in fish liver cells by comet assay. The DNA damage was quantified as; tail length, DNA percentage in tail, tail moment and number of cells with tail. Genotoxicity was severe in Solea vulgaris than Tilapia zillii. Bacterial infections; Vibrio alginolyticus (21 isolate), Aeromonas hydrophila (13), Photobacterium damselae subsp. piscicida (7) were detected in fish specimens. Parasitic Isopoda sp. were found attached to the ventral body surface and inside the gill chamber of fish. Conclusion: The results of this study indicate that Lake Qarun is contaminated with substances that are genotoxic to fish as well as predispose fish to numerous opportunistic pathogens.