Recently, systemic fungal infections have emerged as significant causes of fish mor-bidity and mortality. Hence, the current study investigates the occurrence of somepathogenic systemic fungi inducing severe lesions in the liver and kidneys of Africancatfish. Two hundred diseased African catfish were collected from private fish farmsin Egypt, and only 120 fish were infected with 212 different fungal isolates at a rate of60%. The seasonal survey revealed isolation of 72 isolates of yeast (Candida albicans)and 140 isolates of moulds including non-pigmented moulds, Aspergillus ochraceousand Aspergillus flavus, as well as pigmented mould (Cladosporium herbarum). The iso-lated fungi induced characteristic post-mortem lesions. To date, this is the first reportfor isolation of C. herbarum and C. parapsilosis from Nile catfish liver and kidneys.Various techniques were performed to identify the fungi including gross observa-tion, microscopic examination of tissue squashes, in vitro culture and histopathology.Koch's postulate was fulfilled to confirm the fungal pathogenicity. The challengedfungi altered the hepatorenal indicators (ALP, AST, ALT, urea and creatinine) and oxi-dative stress biomarkers (MDA, CAT and SOD). The results indicate the virulence of the isolated fungi, and future studies are needed for treatment trials.