Oxidative stress is the fundamental etiology of inflammation and organ failure, and unfavorable consequences characterize critical illness. We searched systematically up to September 2021 to find related randomized controlled trials (RCTs) that investigated the effects of selenium in antioxidant markers of the critically ill. A total of 10 RCTs were included. The results indicated that selenium administration has no significant effects on glutathione peroxidase activity (standardized mean difference [SMD]: 1.67, 95% confidence interval [CI]: −0.01 to 3.35) and C-reactive protein levels (SMD: −0.21 mg/L, 95% CI: −0.45 to 0.03). Further trials are needed to prove the potential effects of selenium administration on antioxidant and inflammation markers.