The hypothalamic-pituitary-adrenal (HPA) axis is essential for adaptation to stress. In the present study, we examined the hypothesis that head cooling with mild systemic hypothermia would adversely affect fetal adrenocorticotropic hormone (ACTH) and cortisol responses to an asphyxial insult. Chronically instrumented preterm fetal sheep (104 d of gestation, term is 147 d) were allocated to sham occlusion (n = 7), 25 min of complete umbilical cord occlusion (n = 7), or occlusion and head cooling with mild systemic hypothermia (n = 7, mean +/- SEM esophageal temperature 37.6 +/- 0.3 degrees C vs 39.0 +/- 0.2 degrees C; p < 0.05) from 90 min to 70 h after occlusion, followed by spontaneous rewarming. During umbilical cord occlusion, there was a rapid rise in ACTH and cortisol levels, with further increases after release of cord occlusion. ACTH levels returned to sham control values after 10 h in both occlusion groups. In contrast, plasma cortisol levels remained elevated after 48 h in both occlusion groups and were still significantly elevated in the hypothermia-occlusion group 2 h after rewarming, at 72 h, compared with the normothermia-occlusion and sham groups. In conclusion, hypothermia does not affect the overall HPA responses to severe asphyxia in the preterm fetus but does prolong the cortisol response.