Pseudoplatystoma punctifer is an Amazonian catfish highly appreciated for its high flesh quality, size, and commercial value. Its aquaculture is pursued to satisfy the demands of an increasing population in the region. However, knowledge of the nutritional needs during the early life stages is necessary for improving growth and reducing the incidence of cannibalism, factors that limit the success of its commercial farming. This study aimed at evaluating the influence of four diets containing different protein and lipid levels (30:15, 30:10, 45:15, or 45:10 in %) in the digestive physiology and performance of early juveniles. The results showed that the dietary protein:lipid as well as carbohydrate levels and ratios influenced differently the whole-body proximate composition, the digestive physiology and development, and hence growth and survival. The 45:15 diet promoted the best growth, survival, and the most rapid development of the digestive system, as shown at histological (higher number of hepatocytes, goblet cells in the anterior intestine and enterocytes in all intestinal portions, and longer folds in the posterior intestine), molecular (highest amylase, lipoprotein lipase, phospholipase, trypsinogen, and pepsinogen gene expression), and biochemical (highest lipase and pepsin activities and higher alkaline phosphatase:leucine alanine peptidase activity ratio) levels. Lipids were favored over carbohydrates as source of energy, with lipids promoting a protein-sparing effect at adequate energy:protein ratio. Carbohydrate content higher than 25% was excessive for this species, leading to unbalanced lipid metabolism and fat deposition in the liver.