Selenium (Se) is an essential trace element that plays a pivotal role in many of the body's regulatory and metabolic functions, especially during times of stress. After uptake, Se is incorporated into several Se-dependent proteins, which have potent antiinflammatory and antioxidant capacities. Several observational clinical studies have demonstrated that Se deficiency can cause chronic cardiovascular diseases and aggravate organ dysfunction after cardiac surgery and that low levels of Se may be independently associated with the development of organ dysfunction after cardiac surgery. Based on these findings, several studies have investigated the effects of a perioperative Se supplementation strategy. Therefore, the present review describes in depth the pathophysiology and harmful stimuli during cardiac surgery, how Se may counteract these injuries, the different types of Se supplementation strategies that have been evaluated, and current evidence of its clinical significance. (Nutr Clin Pract. 2019;34:528-539)