This study evaluated the effect of biofloc technology (BFT) at 3 (lsBFT) and 35 (hsBFT) practice salinity units (psu) on the zootechnical performance, oxygen consumption, antioxidant activity, and oxidative damage of Litopenaeus setiferus juveniles reared in outdoor tanks. After 90 days, no significant differences were observed in terms of survival (p > .05). The final weight as well as wet weight gain, final biomass, and feeding conversion ratio (FCR) showed higher values for shrimp reared with hsBFT than those reared with lsBFT (p < .05). Compared to that for the hsBFT treatment, high oxygen consumption (VO2) was observed for the lsBFT treatment under fasting and postprandial conditions (p < .05). The activity of the enzymes catalase, superoxide dismutase, and glutathione‐S‐transferase from shrimp muscle did not show significant differences between the treatments (p > .05). Regarding the lipid peroxidation (LPO) and oxidized protein (PO) in muscle samples, no significant differences were observed in LPO, whereas the PO was significantly higher for the lsBFT treatment (p < .05), which was related to higher fasting and postprandial oxygen consumption of the juveniles (p < .05). The adaptation of L. setiferus juveniles reared in BFT at low salinity is relatively weak because of their low growth and excessive oxygen consumption and the oxidative damage (PO) produced.