The present study was designed to investigate trypanosomiasis among one of native freshwater fish breed in Egypt namely catfish (Clarias gariepenus). Fifty fish were collected during summer season from the river Nile at Giza markets. The fish were examined for the presence of trypanosoma in the blood. Trypanosoma were detected in 10 (20%) of the collected fish. The main clinical signs of infected fish with trypanosoma were emaciation, dullness, respiratory distress, loss of escape reflex, mild ascitis and paleness of the gills. Post-mortem examination of infected fish revealed paleness of the internal organs (liver and kidneys) and slight congestion of spleen. Haematological examination of infected fish revealed significant decrease in erythrocytic count, haemoglobin and packed cell volume but significant increase in total leucocytic count accompanied with neutrophilia and eosinophilia. Serum biochemical analysis demonstrated a significant decrease in urea, total protein and albumin while a significant increase in AST, ALT, ALP, creatinine, glucose and 1- globulin were recorded. Microscopic examination of organ histopathological sections revealed cloudy swelling of hepatocytes with activation of kupffer cells, depletion of lymphocytes with thickening of tile trabeculae in spleen. While in kidney, necrobiotic changes of epithelial lining of renal tubules with vacuolation of glomeruli as well as hemorrhages were recorded.