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The oxidative stress is recognized as a constant feature in critical illness. Nevertheless, the use of antioxidant therapy remains controversial. We tried to demonstrate that intravenous selenium supplementation could promote antioxidant status and help protect against infection and organ failure, improving outcome in critically ill patients.We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the exogenous supplementation of selenium versus standard therapy without any adjuvant in critically ill adults.Nine RCTs met inclusion criteria. Selenium supplementation was associated with a reduction in 28-day mortality of borderline statistical significance (risk ratio = 0.84, 95% confidence interval 0.71–0.99, P = .04). The analysis of pre-defined subgroups detected no significant effects regarding the supplementation with doses of selenium ≤ 500 μg/d, administration of a load dose with a bolus and duration of treatment. Only 2 studies analyzed 6-month mortality and could not show a difference. No effects could be demonstrated on hospital length of stay, pulmonary infections, or renal failure.The use of high-dose selenium might be associated with a beneficial effect on 28-day mortality in critically ill patients. Nevertheless, the use of selenium as adjuvant therapy needs further evaluations.