Saline-tolerant hybrid red tilapia Oreochromis sp. has shown benefits in the aquaculture industry, hence understanding the adaptability to salinity changes is crucial towards developing optimum culture practices. The present study investigates the growth performance and metabolic response of acute and chronic salinity exposure of first-feeding hybrid red tilapia larvae. Acute transfer of larvae from freshwater to six different salinities ranging from 0, 4, 8, 12, 16, 20 g L−1 were performed and continuously cultured for 30 days to determine their chronic effects. Larval exposure to acute 20 g L−1 salinity was lethal, while at 16 g L−1, 55.6 ± 5.1% larvae survived after 24 h exposure. All larvae survived until 30 days at salinity 0 to 12 g L−1. Weight gain, specific growth rate and feed intake were higher at 16 g L−1, corresponded to low feed conversion ratio. Metabolic oxygen consumption was similar between acute and chronic when transferred from 0 to 4, 8 and 12 g L−1, but was higher for acute transfer to 16 and 20 g L−1. Overall, ammonia excretion was significantly higher in acute rather than in chronic exposure. During acute transfer, ammonia excretion increased as the salinity increased but remained constant at chronic exposure. Contribution of nutrient energy during aerobic metabolism (ammonia quotient) and oxygen/nitrogen ratio demonstrated higher protein and lipid utilization during acute transfer, while lipid and carbohydrate were more pronounced during chronic exposure. This study suggests higher metabolic cost during abrupt transfer of hybrid red tilapia to 16 and 20 g L−1 with negative effects on growth performance, but showed ability to recover at 16 g L−1 during 30 days of chronic exposure. Therefore, immediate salinity changes up to 12 g L−1 were tolerable in first-feeding red hybrid tilapia larvae.