Alterations in body temperature may be frequently observed in patients and experimental animals. Systemic infections may alter the host body temperature, and a pre-existing altered body temperature may modulate the host response to infection. Septic patients who develop hypothermia have a significantly worse outcome than those who develop a fever or maintain a normal body temperature. Perioperative hypothermia may occur as a result from anesthetic action, surgical procedures, or specific targeted interventions. This perioperative hypothermia is associated with adverse outcomes including increased surgical wound infections. In animal models of sepsis, perioperative hypothermia is also associated with a worse outcome and specific alterations of the inflammatory response. Understanding the mechanisms of why the host response to infection is impaired by pre-existing hypothermia will both improve our basic understanding of disease as well as identify potential targets for modulation.