Fever is an adaptive response to infections which occurs widely in the animal kingdom. The suppression of fever increases the risk of mortality in animals, although the effect of antipyretics in critically ill patients is unknown. The objective of this study is to determine whether paracetamol influences the risk of mortality in critically ill patients with sepsis. A phase 2b double blind randomised placebo controlled trial of paracetamol will be undertaken in 700 patients with sepsis in six ICUs in New Zealand and two ICUs in Australia under the auspices of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG). If either the aggressive or permissive antipyretic regimes influence outcomes including survival in severe sepsis, the findings will have a major impact on the burden of infectious disease in New Zealand and internationally.