The prognosis of extensively burned patients is dependent upon the presence of sepsis. The more extensive the burns, the more likely patients are to become septic. Although recently the frequency of burn wound sepsis has been decreased due to the early excision of necrotic tissue, that of sepsis resulting from respiratory tract infection has increased. Staphylococcus aureus (methicillin-resistant S. aureus) and Pseudomonas aeruginosav are the agents most likely to cause infections. Sepsis syndrome also results from bacterial translocation (BT), in which gut bacteria and/or endotoxins are thought to enter the portal bloodstream and/or lymphosystem. The pathophysiological mechanism of sepsis is the increased release of inflammatory mediators and resulting imbalances between these substances and their antagonists. In cases of severe sepsis, the sequelae of the imbalance between inflammatory mediators and their antagonists can lead to endothelial injury, DIC, and finally MODS. Strategies against the occurrence of sepsis include hospital-wide infection control measures, blockage of infection routes, and administration of antibiotics. The early initiation of nutritional management, preferably by the enteral route, to enhance immune system function and minimize the occurrence of BT is recommended. Several drugs to control inflammatory mediator release are currently under development and are expected to be used clinically in future.