Salinity refers to the concentration of dissolved salt within water which is a determining factor to influence fish growth. This study aimed to evaluate the effect of selected salinity on the osmoregulation and the growth performance of the juvenile Malabar grouper Epinephelus malabaricus, a high commercial value species in Asian market, and to determine appropriate salinity for maximizing its production. Fish were reared under conditions of temperature at 26oC and photoperiod (LD = 14:10) with different salinities (5, 11, 22, and 34 ‰) for 8 weeks. Salinity had little impact on the plasma Na+ concentration, although the transcript levels of Na?/K?-ATPaseα in the gill was significantly lower in fish reared at 11 ‰. Low oxygen consumption was seen in fish reared at 11‰. Feed conversion ratio (FCR) was lower in fish at 5 and 11‰ than at 22 and 34‰. However, specific growth rate (SGR) was higher in fish at 11‰. These results suggest that rearing fish at 11 ‰ could decrease energy consumption in respiration and improve food conversion efficiency. When fish were reared at 11 ‰, the transcript levels of growth hormone (GH) in the pituitary and its receptor (GHR) and insulin-like growth factor I (IGF-I) in the liver were upregulated, suggesting that the growth axis is stimulated in low salinity conditions. On the other hand, there was little difference in the transcript levels of neuropeptide Y (NPY) and pro-opimelanocortin (POMC) in the brain of fish reared at any salinities, suggesting that salinity had low impact on alternation of appetite. It is concluded that high growth performance is obtained when fish are reared at 11‰ by activating the GH-IGF system, but not the appetite system, of the Malabar grouper juveniles.