Abstract: Dissolved oxygen (DO) is vital in aquaculture, which influences the survival and growth of red swamp crayfish, Procambarus clarkii. To reveal the profiles of antioxidant and energy metabolism in response to acute hypoxia/reoxygenation stress, the activity of some key enzymes associated with antioxidant and non-specific immunity were measured and the ultrastructure changes in the hepatopancreas and gill were observed. Experimental crayfish with average body weight of (26.5±1.8) g were subjected to acute hypoxia stress (DO 1.0±0.1 mg/L), followed by reoxygenation (DO 6.8±0.2 mg/L). Hepatopancreas, gill and hemolymph from five groups of crayfish (six crayfish per group), including normoxia, hypoxia for one and six hours, and reoxygenation for one and 12h, were used to measure the changes of antioxidant and non-specific immunity enzymes. Cell ultrastructure of gill and hepatopancreas were also examined by transmission electron microscope. The results showed that the activity of superoxide dismutase (SOD) in hepatopancreas and hemolymph decreased significantly under hypoxia stress (P<0.05), while it increased significantly in hepatopancreas, hemolymph and gill in the reoxygenation stage (P<0.05). The significant increase of SOD activity may be related to the excessive production of superoxide anion (ROS) in the reoxygenation process. The content of malonaldehyde (MDA) in hemolymph and gill tissue was significantly higher than that of the control group (P<0.01), indicating lipid peroxidation occurred in cells under hypoxia/reoxygenation stress. Under hypoxic stress, the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) in hepatopancreas, gill and hemolymph were both significantly increased (P<0.05), and the activities of ACP in hepatopancreas and gill tissue were significantly decreased after reoxygenation for 12h (P<0.01). These results suggested that hypoxic-reoxygenation stress may affect the immune response of the crayfish. Compared with the control group, lactic dehydrogenase (LDH) content and total ATPase activity in hepatopancreas, hemolymph and gill tissue were significantly increased under acute hypoxic stress (P<0.05), indicating that the energy metabolism function of cells was seriously affected. Observation of mitochondria ultrastructure revealed that the organization structure of gill and hepatopancreas were seriously injured after acute hypoxic/reoxygenation stress. Mitochondrial damage, including mitochondria dissolved into vacuole, mitochondria swelled irregularly and their cristae fractured and become fuzzy. During hypoxia/reoxygenation stress, the number of mitochondria in hepatopancreas cells significantly increased while the number of lysosomes decreased significantly. The results showed that hypoxic-reoxygenation stress can cause great damage to the hepatopancreas and gill of P. clarkii, and affect the activities of antioxidant and non-specific immunity enzymes. Furthermore, the results indicated that hypoxic-reoxygenation stress has great influence on immune defense ability and energy metabolism function of P. clarkii.