Maintaining body temperature within a narrow range is vital for warm-blooded animals. In rodents, the preoptic area (POA) of the hypothalamus detects and regulates core body temperature. However, knowledge about the thermal regulation center in primates remains limited. Here we show that activating a subpopulation of POA neurons by a chemogenetic strategy reliably induces hypothermia in anesthetized and freely-moving macaques. Comprehensive monitoring of physiological parameters reveals that such hypothermia is accompanied by autonomic changes including a rise in heart rate, skeletal muscle activity, and correlated biomarkers in blood.