In this study, acute hypoxia was applied to two states of yellow catfish (Pelteobagrus fulvidraco) (non-feeding and feeding) for 48 h. We investigated the effects of acute hypoxia on the respiratory metabolism and digestive ability of yellow catfish (mean body length: 7.61 ± 0.52 cm). The results indicated that the respiratory frequency of yellow catfish under acute hypoxic post-feeding condition was rapidly accelerated and the oxygen consumption rate was reduced. The level of succinate dehydrogenase in the gills first increased and then significantly decreased (p < 0.05) and the level of lactate dehydrogenase significantly increased (p < 0.05). When the expression level of hypoxia-inducing factor was significantly increased (p < 0.05), the downstream coding genes (hexokinase 1 (hk1), phosphofructokinase (pfkla), and pyruvate kinase M1/2a (pkma)), key molecules of glycolysis, and the activity of crucial enzymes (hexokinase, phosphofructokinase, and pyruvate kinase) increased. At the same time, the glucose level dropped and the lactic acid level increased, indicating that the metabolic mode in the gills of yellow catfish under acute hypoxic post-feeding condition gradually changed to anaerobic, and the anaerobic glycolysis process was activated to provide the required energy for the body. In addition, we found that the activity of digestive enzymes (trypsin, lipase, and amylase) and expression levels of digestive genes (trypsin, lipase, and amylase) were inhibited in the liver and intestine of yellow catfish under the acute hypoxic post-feeding condition, indicating that their digestive ability was reduced. This may adversely affect growth and development. This study analyzed the effects of acute hypoxic post-feeding exposure on the respiratory metabolism and digestive capacity of yellow catfish, providing new insights into fish physiology and sustainable fish culture.