ABSTRACT Aim: Therapeutic hypothermia after perinatal asphyxia decreases brain injury in newborns, whereas hyperthermia worsens the brain injury. We examined how different clinical practices influence regional brain temperatures during hypothermia. Methods: Six newborn pigs, which have comparable physiology and brain maturation to human term infants, were maintained at hypothermia (33.5degC) or normothermia with a servo-controlled whole-body cooling device that is in clinical use. Pigs were anesthetized and fully instrumented for cardiovascular and temperature (rectal and regional brain) monitoring. Changes in brain temperatures were measured during four different paradigms to mimic different clinical practices. Results: Inserting an insulating pillow between the head and the heated surface reduced cortex temperature by 1 or 2degC during normothermia (core temperature Tcore 37degC or hypothermia, Tcore 33.5degC. Reducing ambient temperature from 28degC to 23degC reduced cortex temperature by 3.94 ± 1.9degC. Without a hat and overhead heater at normothermia, cortex and deep brain temperatures were reduced by 1.2 ± 0.8 and 0.7 ± 0.7degC, respectively. Direct overhead heating abolished the normal cortex to deep brain temperature gradient that was maintained if using a head shield. Conclusion: Brain temperature may differ from core temperature during therapeutic hypo-thermia influenced by different clinical practices.