Exposure to any type of stressors either environmental, chemical or perceived stressors, results in a series of physiological responses in animals. The purpose of this study was to investigate the effects of thermal stress on physiological responses in red hybrid tilapia. Adult red hybrid tilapia were previously exposed to gradual increment of water temperature in thermoregulated recirculating tanks at a rate of 1oC/8 h from 28 to 31oC and kept for 1, 7 and 14 days. Cortisol, HMG-CoA reductase, total protein and osmolality were determined. Plasma cortisol and HMG-CoA levels were significantly increased in the heat-stressed groups compared to nonstressed groups. Osmolality was also significantly higher (p