Sepsis or systemic inflammatory response (SIRS) to infection or to non-infectious stimuli such as trauma, surgery, pancreatitis or ischemia, is an increasingly common cause of morbidity and mortality in patients on intensive therapy unit (ITU). In critically ill patients, this accounts for 10% to 50% of all deaths. Oxidative stress has an important role in the development and manifestations of SIRS. Oxidative stress is an imbalance between the free radical production and the antioxidant defense. In critical illness, overwhelming inflammatory mediator response to infective or non-infective stimuli results in excessive production of free radicals (FR). The action of FR is normally limited by the antioxidant defense system of the body, but in critically ill patients the antioxidant capacity is likely to be compromised. Hence, provision of antioxidants to critically ill patients may help in removing the FR and therefore improving the clinical outcome. However, no study has yet provided conclusive evidence of the beneficial effect of antioxidant supplementation in critically ill patients. The clinical evidence provided so far shows that there are several factors which might determine the efficacy of antioxidant supplementation in critically ill patients. There is a need for large multicentre prospective randomized control trials to assess the effects of different types and doses of antioxidant supplementation in selected groups of patients with different types of critical illness.