Thermoregulation and fever are primarily mediated through the hypothalamus and its effector mechanisms. In persons with complete spinal cord injuries above T-6, thermoregulation is substantially impaired because of the interruption of neuronal pathways to and from the hypothalamus. These same pathways are important in the production of fever in response to infections, and injury to these pathways in patients with high-level spinal cord injuries should diminish their ability to mount a febrile response. In clinical practice, however, measurements of body temperature are used to make decisions in patients with spinal cord injuries in a manner similar to that in patients without spinal cord injuries. In this article, we review the literature on thermoregulation and fever in normal persons and in those with complete spinal cord injuries and propose possible mechanisms for fever in persons with high-level spinal cord injuries.