A growth trial was conducted to detect the effects of different diets on the growth performance and hypoxia adaptation capacity of Mississippi Paddlefish (Polyodon spathula) larvae. The larvae were fed with live food, formulated diets, and 1/2 live food with 1/2 formulated diets. After a 15-d growth trial, final body weight and total body length were measured, and five larvae from each dietary group were subjected to 1 h of hypoxia treatment. Serum total antioxidant capacity (T-AOC), serum superoxide dismutase (SOD), and liver malondialdehyde (MDA) were measured. Final body weight and weight gain of the fish fed live food were significantly higher than the values for the other two groups. Total body length of the fish fed live food and 1/2 live food with 1/2 formulated diets exhibited no significant difference. After hypoxia treatment, serum T-AOC and SOD activities of the fish fed formulated diets were significantly lower than those of the other two groups. Liver MDA content of the fish fed with live food was significantly higher than that of the other two groups. In conclusion, larval paddlefish fed with an appropriate proportion of live food and formulated diets exhibit improved adaptive capacity to hypoxia.