An experimental ecological method was used to determinate the effects of hypoxia on the median lethal time (LT₅₀) and physiological function of two sizes of sea cucumber (large-size:with a body weight ranging from 28.00 g to 36.00 g; small-size:with a body weight ranging from 9.00 g to 13.00 g) at high temperature (25℃). The LT₅₀ in the two sizes of sea cucumber at a dissolved oxygen (DO) concentration of 1 mg/L were investigated. The diurnal metabolism in the two sizes of sea cucumber at DO concentrations of 1, 3, and 6.5 mg/L (normoxia) were estimated. The glutathione (GSH) content and activities of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capability (T-AOC) in the coelomic fluid and respiratory tree, as well as the cortisol level in the coelomic fluid at 24 h hypoxia stress (the DO concentrations of 1 mg/L and 3 mg/L) and 72 h reoxygenation of the two sizes of sea cucumber were also measured. The results showed that, at first, at the DO concentration of 1 mg/L, the LT₅₀ for the large and small-size sea cucumber was 33.37 h and 28.84 h, respectively. The metabolism in the two sizes of sea cucumber was significantly lower than that in the normoxia condition (hereafter control), the overnight metabolic intensity was higher than during the daytime, and metabolic intensity in the small-size sea cucumber was higher than in the large-size one. Secondly, during the 1 mg/L hypoxia stress, the variations of the four antioxidant indices in the coelomic fluid in the large-size sea cucumber and those in the respiratory tree in both sizes of sea cucumber were similar:compared with the control group, the hypoxia exposure decreased the content of GSH and the activity of SOD and T-AOC, but increased the activity of CAT. However, at the end of the hypoxia stress, the content of GSH and the activity of SOD, CAT, and T-AOC showed no significant difference from the control group. After 72 h of reoxygenation, the above four antioxidant indexes of the coelomic fluid in the two size groups of sea cucumber recovered to the level of the control group but the four antioxidant indexes of the respiratory tree did not. During the 3 mg/L hypoxia, the variation trend of the four antioxidant indexes in the coelomic fluid and respiratory tree of sea cucumber was consistent with those in the 1 mg/L group. After 72 h of reoxygenation, the above four antioxidant indexes of the coelomic fluid in sea cucumber recovered to the level of the control group. Except for T-AOC, the other three indices of the respiratory tree also recovered. The recovery ability of the small-size sea cucumber was higher than that of the large one after hypoxia stress. Thirdly, at the DO concentrations of 1 mg/L and 3 mg/L, the content of cortisol in the coelomic fluid of both sizes of sea cucumber was significantly higher than the control group at the end of the stress (<0.05). The level of cortisol in the coelomic fluid of the large-size sea cucumber was higher than in the small one but both recovered to the control level after reoxygenation. The results showed that if the hypoxia duration is less than the LT₅₀(24 h, for example, in this paper), sea cucumber can alleviate the oxidative damage. However, if the time under hypoxia exceeds the threshold value, sea cucumbers will suffer irreversible damage and die.