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Oxidative stress after burn injury induces inflammatory and hypermetabolic responses associated with adverse outcomes. We propose that antioxidant and trace element supplementation may reduce oxidative stress and subsequently alleviate inflammation and hypermetabolism, thus improving clinical outcomes. We conducted a cohort study of adult patients with an acute burn injury admitted to our provincial burn center. Patients in the antioxidant group received an intravenous infusion of multivitamins and trace elements for the first 14 days after admission. The inflammatory profile was assessed at early time points, < 14 days postburn, and later time points, ≥ 15 days postburn, and included interleukin (IL)-1β, interferon-γ, IL-1 receptor antagonist, IL-6, granulocyte-macrophage colony-stimulating factor, and FMS-like tyrosine kinase 3 ligand. Hypermetabolism was assessed by resting energy expenditure. Clinical outcomes included mortality, morbidities, hospital length of stay, and infections including days to the last positive culture after injury. We studied 172 patients, mean age 49 ± 17 years and 33 ± 13% TBSA burned, with 91 controls and 81 patients in the antioxidant group. Patients in the antioxidant group had significantly lower levels of inflammatory markers at both early and late time points, P < .05. Antioxidant treatment was associated with decreased measure of hypermetabolism, P < .05. Morbidity and mortality were not significantly different between groups. Length of hospital stay was significantly shorter in the antioxidant group when adjusted for patient demographics and injury characteristics (RR, 0.78; 95% CI, 0.66–0.92). In the antioxidant group, while infections were not different, the last positive culture post-injury was documented at median 19 days (IQR, 11–43 days) compared with controls at 35 days (IQR, 15–59 days), P = .012. Patients receiving antioxidant and trace element supplementation had reduced markers of burn stress–induced inflammation; they were also associated with a decreased hypermetabolic response, shorter length of stay, and improved bacterial clearance.