Global warming is shifting the population of animals around the world, due to the frequent extreme heatwaves. Scientists anticipate that the ocean temperature will rise by 1-4°C by the year 2100. Fishes as an ectotherm are particularly vulnerable to global warming. However, there is limited information about the possible impact of global warming on fish physiology. This study was designed to investigate and compare the effects of long-term thermal acclimation on antioxidant enzymes activities and the potential stress in blue tilapia (O. aureus) (20±1.7 g). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR), as well as γ -glutamyl cysteine synthetase (γ -GCS) and γ-Glutamyl transferase (γ-GT). In comparison to fish acclimated to winter ambient temperature, the activity of the liver and white muscle enzymes increased dramatically in fish adapted to 30°C and 40°C. While the levels of lipid peroxidation (LPO) were significantly increased in tissues of fish acclimated to 40°C, as compared to fish at both ambient and 30°C.