This study investigated the effects of different combinations of protein and carbohydrates on growth performance, body composition, blood and liver biochemical parameters, and intestinal enzyme activities of Rhamdia quelen. The jundiá (4.03 ± 0.02 g) were divided into groups with each group fed for 40 days with a diet as follows: casein + corn starch (CASCS), casein + fructose (CASFRU), gelatin + casein + maltodextrin (GCASMALDEX), fish meal + corn starch (FMCS), and fish meal + fructose (FMFRU). After this period, significantly higher growth was observed in fish that were fed the FMCS diet. In addition, the fish in the FMCS treatment group exhibited higher levels of amino acids, cholesterol, glucose, and plasma proteins, higher activity of lipase and lower activity of chymotrypsin and trypsin, and higher protein and lipid retention than those in other treatments. The digestive somatic index of the fish on the CASFRU diet increased significantly throughout the experimental period. Increased activity of maltase in the jundiá that received the CASCS diet, and alanine aminotransferase in the fish receiving the FMFRU treatment were observed. In conclusion, the jundiá that received the FMCS diet showed better digestive and metabolic efficiency and consequently better growth performance.