We evaluated the combined effects of temperature and salinity on the energy metabolism of Nile tilapia juveniles (GIFT strain). We used a two-factor central composite experimental design (CCD) and response surface methodology (RSM) to test the effects of temperature (13–36excretion rate () under laboratory conditions. The linear effects of temperature and salinity, the quadraticsalinity, and the interaction between salinity and temperature had significant effect on ). The quadratic effect of temperature was not associated with changes in >0.05, <0.01), and could be used for prediction. The were influenced more by temperature than by salinity. At lowerOR, were higher around the iso-osmotic point. However, when salinity exceeded the iso-osmotic point, but vary with salinity ( and salinity range of 0–10, tilapia juveniles utilized protein-lipirespiratory quotient value was 0.752. Our results provide insight into the joint influence of temperature and salinity on the metabolism of tilapia juveniles and provides a bioenergetic basis for the study of how environmental factors govern the spatial and temporal pattern of energy distribution in this species.