In this study fish samples were investigated for Bacteria and Fungi, in fish parts, such as intestine, gills and skin. Bacterial counts of Total viable bacteria (T.V.B) reached more than 9.5 × 105 cfu and faecal coliforms (F.C) reached 1.2 × 105 cfu. Different species were identified, Using API technology. Escherichia coli comes first by being recording thirty number case of isolation constituting 36%, it followed by Proteus mirabilis which is represented by twenty four number case of isolation accounting for 30%. Other taxa viz: Klebsiella pneumonia, Citrobacter freundii, Providencia stuartii and Erwinia sp. came next according to their case number of isolation, they represented only by 7%. They showed different antibiotics with different inhibitory concentrations, resistance pattern to gentamycin 10 μg, Penicillin G, tetracycline 30 μg, Ampicillin 10 μg, Ampicillin 30 μg, chloramphenicol (C) 30 μg, Rifampicin 25 μg, Streptomycin 5 μg, cefotaxime 15 μg. Mycological investigation revealed the presence of variety of fungal species, particularly, toxigenic species, such as, Aspergillus spp, Penicillium spp and Fusarium spp. These results are indication of the spoilage of fishes which caught from Lake Manzala and are risky for human consumption and hazardous to human health in this important area of Egypt, due to the high pollution condition of Lake Manzala.