The aim of the present study was to evaluate the effects of dissolved oxygen levels on physiological responses including respiratory metabolism, nutritional physiology, and immunological condition of Portunus trituberculatus. Fifty adult crabs were exposed to different dissolved oxygen levels (1, 2, 4, 8 and 12 mg/L water) for 10 days, and then the oxygen consumption rate, the contents of proteins, oxyhemocyanin (Oxy-Hc) and hemocytes in blood, the metabolites of digestive gland (glycogen, protein, glucose, cholesterol, acylglycerol and lactate), the activities of digestive enzymes and lactate dehydrogenase (LDH) were determined. The results showed that the critical levels of dissolved oxygen for Portunus trituberculatus were between 2 and 4 mg/L. The contents of proteins and Oxy-Hc followed a similar pattern with the oxygen consumption rate. The contents of glycogen and proteins of digestive gland, and the activities of total proteases, trypsin and chymotrypsin were not affected by the environmental dissolved oxygen (P>0.05), but the contents of glucose, cholesterol and acylglycerol were decreased linearly with the decrease of available oxygen in water. The gill LDH activity and the content of lactate in digestive gland rose sharply as the level of dissolved oxygen decreased (P<0.05). Low levels of dissolved oxygen also affected the immune system through reducing the content of hemocytes (P<0.05). Portunus trituberculatus shows a moderate tolerance to low oxygen availability by modifying the contents of Oxy-Hc and some metabolites of digestive gland, and by activating the anaerobic metabolism as well.