A total of one hundred and twenty cat fish (Clarias gariepinus) were collected from two private fish farms in Dakahlia governorate during summer, 2016. We collected fifty diseased fish from first farm which suffered from cumulative mortality and seventy healthy fish from second farm. All collected fish were subjected to clinical, postmortem, histopathological and mycological examination. Aflatoxins were extracted and quantitated from feed and musculature of diseased and healthy fish (5 samples for each) using HPLC. Blood samples were collected for biochemical and hematological parameters. The clinical observation revealed that the diseased fish showed opacity of the eyes, paleness of the gills with presence yellowish greenish infiltration, hemorrhagic, yellowish skin and fins, and the fish were slow in motion. The postmortem examination showed enlargement of the gall bladder, distention of the stomach, yellowish enlarged liver, swollen, dark red and friable kidneys. Whereas the histopathological examination revealed a severe degenerative and necrotic changes in most internal organs of diseased fish. On the other hand mycological examination of diseased fish yielded isolation of Aspergillusflavus (42%), A. parasiticus (34.8%), A. niger (12%) and A. fumigatus (10.9%). While no fungi was isolated from any organs of healthy fish. The mean levels of aflatoxins in feed of diseased fish was  108.9±0.77 ppb (46.5±0.75 ppb AFB₁, 1.4±0.11 ppb AFB₂, 58.9±0.38 ppb AFG₁, 2.1±0.24 ppb AFG₂), while the mean levels of AFs residues detected in musculature of diseased fish was 20.9±0.39 ppb (11.3±0.25 AFB₁, 0.15±0.007 AFB₂, 8.9±0.20 AFG₁, 0.5±0.44 AFG₂). Whereas Aflatoxins not detectable in feed or muscles of healthy fish. Regarding to biochemical and hematological parameters, there were significant decrease in serum protein and albumin also a significant increase in AST, ALT and serum creatinine, as well as there were significant decrease in HB concentration and RBCs count of diseased fish compared to healthy fish.