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Fishmeal (FM) and soy meal (SM) are the most common protein sources used in fish feed, but they are associated with environmental, economic or production problems. Insects could be an interesting alternative source of protein. This work investigates the nutritive value of Tenebrio molitor meal (TM) and the effect of total replacement of SM by TM (TM/FM diet) or partial replacement of FM by TM (TM/FM/SM diet) versus a diet based in SM and FM (FM/SM diet) for tilapia. We studied the chitin content in TM, the in vitro protein digestibility, protease activity, oxidative stress and antioxidant defences, growth performance and nutrient utilization. The results indicate that an inclusion up to 500 g kg−1 of TM in the diet did not affect feed intake, in vitro protein digestibility, muscle amino acid composition or biometric indexes. However, their inclusion reduced growth performance and affected the muscle fatty acid profile. The lowest values for protease activity, elevated FRAP in digestive tracts and ROS level in muscle and higher SOD activity were observed in fish fed with SM/FM diet. The use of TM requires better understanding of the role of chitin in digestion and the study of toxins that might affect fish growth.