This study tested the hypothesis that the sexually dimorphic adrenocortical response to stress is already established before birth. Chronically instrumented late gestation pregnant sheep carrying 16 male and 15 female age-matched singleton fetuses were subjected to an acute episode of hypoxic stress. Maternal and fetal blood gases, adrenocorticotrophic hormone (ACTH), and cortisol were measured. In addition, six male and six female fetuses received the ACTH analog, Synacthen, and plasma cortisol was measured. During hypoxic stress, the increment in plasma cortisol was 2-fold greater in male versus females fetuses (30.6 ± 3.2 versus 14.3 ± 2.0 ng/mL; p < 0.001) mediated, in part, by greater adrenocortical sensitivity to ACTH. The data support the hypothesis tested and show that sex-specific differences in the cortisol stress response are present before birth with the output of cortisol being much greater in male than in female fetuses.