This study was carried out on 240 Clarias gariepinus fish collected from The River Nile and El- Ibrahemia canal, Assuit city and the around cities (20 fish /month). The period of study was carried out during October 2011 till the end of September 2012. The clinical finding of naturally infected fish included erosions, ulceration of skin, skin darkening, fin rot, petechial hemorrhage at different parts of the body, necrotic foci and growth of the fungl hyphe in different sites on the skin and fins. It's colour was from white to brown.Mycological examination of collected samples resulted in isolation of 1200 isolates from 240 fish in presence of 960 isolates as mixed cases. The incidence of moulds isolated from fish were Fusarium solani (210)17.5%,  Aspergillus flavus (184)15.2%, Aspergillus niger (170)14.3%, Mucor hiemalis (162)13.5%, Penicillium chrysogenum (97) 8.1%, Penicillium aurantiogriseum (95) 7.9%,  Chladosporium herbarum (85)7.1%, Saprolegnia Sp. (60) 5% , Rhizopus Sp. (54) 4.5%, Chladosporium sphaerospermum (53) 4.4% Acremonium strictum (18)1.5%, Alternaria alternate (12)1%. Bacteriological examination of collected samples resulted in isolation of 370 isolates from 240 fish in the presence of 130 isolates as mixed cases. The incidence of Gram negative bacilli bacterial isolated from fish were Flavobacterium columnare (115)31.1%, Aeromonas hydrophila (75) 20.3%, Edwardsiella tarda (57) 15.4%, Pseudomonas sp. (43)11.6%, E. coli (21)5.7%, Proteus sp. (19) 5.1%, Klebsiella (12) 3.2% . The incidence of Gram postive cocci isolated from fish were Streptococcus sp. (15) 4.1%, Staphylococcus sp. (13) 3.5%. All fish in this study infected by 1-3 types of bacteria with 3-5 types of fungi at the same time.