The use of plant ingredients in aquafeeds for piscivorous fish species is a reality that exposes fish to a number of antinutritional factors present in plants. The present study is the first to evaluate the effect of two purified antinutrients, saponins and phytosterols, in sea bream juveniles. For that purpose, seven diets were formulated: a control diet (fishmeal and fish oil based) and six experimental diets containing low (1 g kg− 1, SapL) or high (2 g kg− 1, SapH) levels of purified soya saponins, low (5 g kg− 1, PhytL) or high (10 g kg− 1, PhytH) levels of purified phytosterols or a combination of 1 g kg− 1 saponins + 5 g kg− 1 phytosterols (SapPhytL) or 2 g kg− 1 saponins + 10 g kg− 1 phytosterols (SapPhytH). Fish were fed for 48 days in order to evaluate growth performance, feed utilization, plasma cholesterol, and gut health as assessed by histomorphological evaluation and gene expression profiling of immune and functional markers. Fish fed the diets PhytH, SapPhytL and SapPhytH showed better feed utilization and PhytH and SapPhytH showed higher protein utilization than the other groups, although this was not reflected in improved growth performance. Histomorphological analysis of the distal intestine revealed increased variation in supranuclear vacuole sizes after 48 days of feeding diets SapH, SapPhytL and SapPhytH and increased number of intraepithelial leukocytes in response to all dietary treatments except SapL and SapPhytL. Although juvenile sea bream growth was not affected by dietary inclusion of saponins and phytosterols, the results indicated some disturbances of the intestinal mucosal structure that could compromise function and/or protection from potential dietary antigens or opportunistic pathogens.