Hypoxia is a common stress phenomenon in aquaculture. Hypoxia tolerance of fish is an important indicator of fish resistance. To study the hypoxia tolerance of juveniles of tiger groupers (Epinephelus fuscoguttatus) and the hybrids, named jinhu groupers (E. fuscoguttatus♀×E. tukula♂), a closed breathing chamber was used to measure the oxygen consumption rate and suffocation point. In addition, the gradual hypoxia method was used to measure indicators of antioxidant enzyme activity and energy utilization in the liver by sampling the liver tissues of the individuals after 1 h at various dissolved oxygen levels [normal (5.71±0.31) mg/L, 4 mg/L, 3 mg/L, 2 mg/L, 1 mg/L, and 0.4 mg/L] and after 3 h at a normoxic level. The experimental results showed that when the water temperature was at (31.18±0.38) ℃, the oxygen consumption rate of jinhu grouper juveniles was 0.16 mg/(g·h), which was significantly higher than that of the female tiger grouper juveniles (P＜0.05). The suffocation points of tiger grouper and jinhu grouper juveniles were 0.22 mg/L and 0.24 mg/L, respectively, and the difference between the two species was not significant. During the process of decreasing dissolved oxygen concentration and returning to normal dissolved oxygen, there was a significant difference (P＜0.05) between superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lactate dehydrogenase (LDH) enzyme activities and lactic acid (LD) content in the liver of tiger grouper juveniles, as well as SOD, catalase (CAT), GSH-Px, total antioxidant capacity (T-AOC), LDH enzyme activities in the liver of jinhu grouper juveniles. However, the activity change of T-AOC and CAT in the liver of tiger grouper juveniles and the content of LD in the liver of jinhu grouper juveniles were not significant. After 3 h of reoxygenation, the activity of SOD in the liver of tiger groupers increased by 16.7% and that of GSH-Px increased by 42.5%, while the content of LD increased by 2.8%. There were significant differences in these indicators between the reoxygnation group and the normoxic group (P＜0.05). However, there were no significant differences in the indicators of jinhu grouper juveniles compared with the normoxic group, except for the activity of GSH-Px (P＜0.05). During the change in dissolved oxygen level, the activation levels of SOD, GSH-Px, CAT, and T-AOC in the liver of jinhu groupers reached 29.1%, 17.9%, 42.4%, and 76.0%, respectively, which were higher than the maximum activation levels of corresponding antioxidant enzymes in tiger grouper livers. The experimental results showed that jinhu groupers had a slightly higher oxygen consumption rate than tiger groupers and that their hypoxia tolerance was higher. Thus, jinhu groupers can be cultured on a large scale and in high density. After being subjected to hypoxia stress, compared with tiger groupers, jinhu groupers could efficiently activate the antioxidant defense system to protect the body from oxidative damage and had a faster recovery ability after hypoxia.