Sander lucioperca is an important cultured fish in Eurasian countries. It has broad breeding prospects owing to its rapid growth, pronounced adaptability, tender flesh, and high nutritional value. However, the farmed production remains limited to only 4.29 kilotons, primarily because of the scarcity of suitable, high-quality compound feeds. This study examined the effects of different dietary protein and lipid levels, and their interactions, on growth, liver histology, antioxidant enzyme activity, and immune-related gene expression in juvenile S. lucioperca. The experiment included two protein levels (51% and 54%) and three lipid levels (12%, 15%, and 18%), thus using six distinct feed formulations. Juvenile S. lucioperca [(1.16±0.01) g] were fed with these formulations during an 8-week feeding trial. The results showed that the dietary lipid level exerted a significant effect on final body weight and specific growth rate of juvenile S. lucioperca (P＜0.05), whereas no significant interaction between protein and lipid levels was observed with regard to final body weight and specific growth rate. At a protein level of 51%, the highest final body weight and specific growth rate were achieved with 18% lipid content; at a protein level of 54%, these metrics were also greatest at the 15% lipid level. As the lipid level in diet increased, the crude protein content in whole fish decreased gradually, whereas the crude lipid content showed an increasing and then decreasing trend. Considerable fatty degeneration of hepatocytes was observed in the 54% protein, 18% lipid group, which was not observed in other treatment groups. At a protein level of 51%, the activities of antioxidant enzymes such as catalase, glutathione, and superoxide dismutase significantly increased with the increase of dietary lipid levels (P＜0.05); at a protein level of 54%, the catalase activity significantly increased with the increase of dietary lipid levels (P＜0.05). The expression levels of complement genes (c3, c4, and c5) and a anti-inflammatory cytokine-related gene (tgf-β) in the liver increased significantly with the increase of dietary lipid levels (P＜0.05), whereas the expression levels of pro-inflammatory cytokine-related genes (il-1β, il8, and tnf-β) decreased significantly (P＜0.05). In conclusion, appropriate lipid levels in diet can improve the growth performance of juvenile S. lucioperca, save protein intake, whereas excessive lipid level may increase the risk of vacuolar degeneration of hepatocytes. It is recommended that the protein and lipid supplementation levels in diet of juvenile S. lucioperca juvenile are 51% and 18%, respectively.