OBJECTIVE: Critical illness is associated with the generation of oxygen free radicals and low endogenous antioxidant capacity leading to a condition of oxidative stress. We investigated whether supplementing critically ill patients with antioxidants, trace elements, and vitamins improves their survival. METHODS: We searched four bibliographic databases from 1980 to 2003 and included studies that were randomized, reported clinically important endpoints in critically ill patients, and compared various trace elements and vitamins to placebo. RESULTS: Eleven articles met the inclusion criteria. When the results of all the trials were aggregated, overall antioxidants were associated with a significant reduction in mortality [Risk Ratio (RR) 0.65, 95% confidence intervals (CI) 0.44-0.97, p=0.03] but had no effect on infectious complications. Studies that utilized a single trace element were associated with a significant reduction in mortality [RR 0.52, 95% CI 0.27-0.98, p=0.04] whereas combined antioxidants had no effect. Studies using parenteral antioxidants were associated with a significant reduction in mortality [RR 0.56, 95% CI 0.34-0,92, p=0.02] whereas studies of enteral antioxidants were not. Selenium supplementation (alone and in combination with other antioxidants) may be associated with a reduction in mortality [RR 0.59, 95% CI 0.32-1.08, p=0.09] while nonselenium antioxidants had no effect on mortality. CONCLUSIONS: Trace elements and vitamins that support antioxidant function, particularly high-dose parenteral selenium either alone or in combination with other antioxidants, are safe and may be associated with a reduction in mortality in critically ill patients.