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 1 o C/8 h from 28 to 31 o C 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<0.05) at day 14 in heat-stressed groups compared to non-stressed groups. Our study demonstrated that exposure to elevated water temperature affect physiological parameters in red hybrid tilapia, thus suggesting a potential threat to its biological performance.