Background: Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming. Methods: Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 °C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 °C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded. Results: During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 ± 0.7 vs. 32.3 ± 0.7 p < 0.05, respectively, 40 minutes: 37.5 ± 0.3 vs. 34.7 ± 0.8 p < 0.05, respectively). Conclusion: Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 °C and NPT should be closely monitored.