Associations between prenatal maternal emotional complaints and child behavioral and cognitive problems have been reported, with different relations for boys and girls. Fetal programming hypotheses underline these associations and state that the early development of the HPA-axis of the children may have been affected. In the present study, differences in cortisol responses of prenatally exposed and nonexposed children are examined for both sexes separately. Cortisol response patterns of a group preschool aged children that were prenatally exposed to high levels of maternal emotional complaints (N = 51) were compared to a nonexposed group (N = 52). Child saliva was collected at the start of a home visit (T1), 22 min after a mother-child interaction episode (T2), and 22 min after a potentially frustrating task (T3). Repeated measures analyses showed that prenatally exposed girls showed higher cortisol levels across the three episodes compared to nonexposed girls. No differences were found in boys. Maternal prenatal emotional complaints might be related to child HPA-axis functioning differently for boys and girls.