Availability of quality feed is one of the most important factors for the best production in aquaculture sector. Despite the great potential, aquaculture has remained underdeveloped in Ethiopia. The study evaluated the effect of increasing animal-based protein in developing compound feed for juvenile Oreochromis niloticus on growth and apparent nutrient digestibility. The study was conducted at the National Fisheries and Other Aquatic Life Research Center (NFALRC), Sebeta, Ethiopia from June 2021 to October 2021. Three treatment diets and a control diet was tested in triplicate tanks in greenhouse conditions. Three iso-nitrogenous (35 % crude protein) diets were formulated. The first treatment was a commercial feed (Alema excellent) which is prepared for fry and fingerling stages of tilapia and was used as a control diet. The other treatment diets contain 22 % animal-based protein and 78% plant-based protein (ABP22), 43% animal-based protein and 57% plant-based protein (ABP43), and 65% animal-based protein and 25% plant-based protein (ABP65). Chromic oxide at an inclusion level of 1% was used as an external marker for the digestibility study. A total of 360 juvenile O. niloticus were stocked in four treatments, each in three replicates using a completely randomized design. A total of 156 juvenile O. niloticus were stocked in triplicate in aquaria for the apparent digestibility study. The results showed that increasing the proportion of animal-based ingredients in the diet significantly affected the growth (P < 0.05) and nutrient digestibility of juvenile O. niloticus. Fish fed with ABP22 diet and the control showed better growth and improved nutrient digestibility. This could be attributed to the use of soybean meal as a major protein source and mixing effect of different plant proteins, which might reduce the anti-nutritional effect, present in plant protein sources. Better carcass composition of the fish was also observed for the control and ABP22 diets than the others. This could be related to the composition of the diets fed, which have direct relationship with body composition of the fish. From the economic point of view, ABP22 feed was found to have the lowest incident cost (48.7) and higher profit index (0.69) than the rest of the diets. The results of the present study indicated promising results on the nutritional and economic factors for increasing plant-based protein in the diet of juvenile O. niloticus in terms of growth parameters, apparent nutrient digestibility, carcass composition, and economic analysis.