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The utilization of plant-based diets in fish is limited by the presence of anti-nutrients, which bind to dietary nutrients and reduce their bioavailability. Exogenous enzyme supplementation may alleviate the effects of anti-nutrients and improve feed utilization. In this study, a commercial multi-enzyme Natuzyme50® was added to a kikuyu-based diet at a rate of 0 (control), 0.25, 0.5, 0.75 and 1.00 g kg−1 DM. Each diet was fed to triplicate groups of Oreochromis mossambicus for 60 days. All fish fed diets containing Natuzyme50® had higher ( P < 0.05) growth performance compared with those fed the control diet. Fish fed the diet containing 0.50 g kg−1 had the best growth performance, highest protein digestibility and the highest levels of digestive enzyme activities. When Natuzyme50® was supplemented above 0.50 g kg−1 in the diet, growth performance and enzyme activities decreased. The improved growth performance observed with Natuzyme50® supplementation was attributed to the presence of enzymes such as cellulase, xylanase and phytase in the cocktail that are not naturally produced by fish. The presence of these enzymes released bound nutrients that would have not been available to the fish. Natuzyme50® supplementation also increased ( P < 0.05) the activities of endogenous enzymes, improving the efficacy of the digestive process. The optimal dietary level of Natuzyme50® for optimal growth performance in O. mossambicus was 0.62 g kg−1 DM feed. Cost benefit analysis indicate that adding up to 0.5 g Natuzyme50® kg−1 in the diet results in higher profits as the increased growth attained offset the additional cost of Natuzyme50®. [ABSTRACT FROM AUTHOR]