This study investigated the metabolic and hematological responses of silver catfish fed diets composed of different protein sources for 90 days. Six different diets were formulated: MBY (meat and bone meal + yeast); SY (soybean meal + yeast); S (soybean meal); MBS (meat and bone meal + soybean meal); FY (fish meal + yeast); FS (fish meal + soybean meal). In the liver, the concentration of glucose, lactate and protein was lower in fish fed SY and S diets. Liver glycogen did not differ between diets. At the muscular level, the glycogen, glucose, lactate content was lower in the FS diet, while the protein decreased in the fish that received the soybean meal-based diet (S). On the other hand, higher values of protein, glucose and lactate were observed in the diet containing meat and bone meal + soybean meal (MBS). The silver catfish fed diets based on fish meal (FY and FS) had a higher protein content in the kidney. Hematological parameters were influenced by diets. The absence of animal protein sources in the diets resulted in lower values of hematocrit and hemoglobin in silver catfish blood. It is concluded that diets containing vegetable and animal protein sources improve the nutritional and health status of silver catfish.