This study investigated the dietary substitution effect of fish meal (FM) with cow blood meal (CBM) on growth performance, feed utilization, haematology and functions of antioxidant enzymes in Clarias gariepinus. In the test diets, FM was substituted with CBM at 7% (CBM1), 17% (CBM2), 25% (CBM3) and 33% (CBM4) inclusions. Feeding trial lasted 51 days after which the biological assays were conducted. Fish fed 7% CBM recorded better growth performance (average body weight, relative growth rate and food conversion ratio), while 33% CBM fed fish performed poorly. Incorporation of CBM in fish had no substantial effect on packed cell volume and white blood cell contents. Additionally, red blood cell count of the fish fed CBM2 decreased markedly, relative to control. When 7% CBM dietary inclusion level was exceeded in experimental feed formulation (CBM 2, 3, 4), the activities the following antioxidant enzymes: superoxide dismutase, catalase and glutathione peroxidase declined considerably, while glutathione reductase and reduced glutathione activities elevated significantly. Malondialdehyde contents elevated prominently in CBM 2, 3 and 4 groups compared to CBM1 and the control. Dietary incorporation of CBM of more than 7% negatively affected growth, feed utilization, altered antioxidant enzymes functions and malondialdehyde levels in C. gariepinus.