The oxygen consumption and wellbeing of hybrid grouper Epinephelus fuscoguttatus × E. lanceolatus (TG × GG) juveniles were evaluated after 60 days of being exposed to different salinities (10, 15, 20, 25, and 30 psu) in triplicate (20 fish / tank; 55.0±1.0 g body weight; 12.0±0.5 cm total length). The fish were fed daily with commercial pellet (42% protein, 9% ash, and 11% lipid).Results showed that the oxygen consumption rate (OCR)was significantly lower at15 psu but higher at 25 and 30 psu, indicating the high metabolic rate of fish in high salinities. The fish's wellbeing was monitored through growth and blood parameters. The fish cultured at 15 psu grew better in terms of final body weight, specific growth rate (SGR), feed efficiency (FE), and condition factor (CF) as compared with the fish at other salinities. Blood hematologic parameters were significantly higher in 15 psu but lower in 25 and 30 psu, whereas blood biochemical parameters were significantly lower in 15 psu but higher in 25 and 30 psu compared with other salinities. Overall, the TG × GG hybrid grouper showed the best OCR and wellbeing when cultured in 15 psu salinity. The findings will be useful in further studies on the management of TG × GG hybrid grouper.