Climate change poses significant challenges to the expansion of aquaculture production. Environmental stressors such as rising water temperatures, increased incidence of heat waves, and water salinization limit the growth of this industry. Identifying practical strategies to mitigate such effects is crucial for enhancing the sustainability of aquaculture. The present study aimed to evaluate the potential benefits of dietary selenium supplementation in Nile tilapia, Oreochromis niloticus, reared in brackish water for nine weeks, followed by a four-day heat stress challenge. Fish were fed diets containing 0 (control), 0.5, 1, and 2 mg/kg selenium nanoparticles in triplicate groups during nine weeks of rearing. Results indicated that dietary selenium significantly improved growth performance, feed efficiency, survival rates, and intestinal activities of digestive enzymes. Dietary selenium also improved various antioxidant and immunological parameters in plasma, intestine, and liver. Selenium supplementation boosted hepatic glutathione peroxidase, reduced glutathione, and total antioxidant capacity, before and after heat stress. Dietary selenium effectively mitigated stress-induced increases in plasma glucose, alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde. While heat stress elevated plasma cortisol and decreased plasma T