There has been a growing interest in micronutrients as a result of their essential role in endogenous antioxidant defense mechanisms and immunity. Critically ill burn and trauma patients are characterized by an increased free radical production, which is proportional to the severity of the injury. In addition, they are at high risk of negative trace element balances, which contribute to the imbalance in endogenous antioxidant capacity and the extension of primary lesions. Although selenium, zinc, and vitamin C and E status are altered in all injured patients, patients with major burns are unique for having copper deficiency. In major burns, high-dose ascorbic acid for 24 hours achieves reduction of resuscitation fluid requirements by endothelial antioxidant mechanisms both in animal models and in 1 human trial. Supplementation trials in trauma and burns including selenium and zinc have shown that early provision of micronutrients improves recovery. Vitamin supplementation trials without selenium have not achieved definitive effects. The human studies show that reinforcing antioxidant defenses early in the course of major injury is rational and that substituting the large initial micronutrient losses of selenium and zinc is safe in trauma, as is the addition of copper in burns. The IV route seems the only way to deliver the doses required to obtain a clinical effect.