Centrally released oxytocin (OT) is believed to attenuate the response of the hypothalamic pituitary adrenal (HPA) axis to psychogenic stress. To test this hypothesis, we measured plasma corticosterone concentrations and Fos immunoreactive protein in the paraventricular nucleus of the hypothalamus (PVN) and limbic brain areas of female wildtype and OT knockout mice that were exposed to a shaker platform, a predominantly psychogenic stress. Plasma corticosterone concentrations following shaker stress were higher in female OT knockout mice than wildtype mice. Genotypic differences in the corticosterone response after shaker stress persisted across all stages of the estrous cycle and when mice were conditioned to repeated shaker stress. Shaker stress activated Fos in OT-positive neurons of wildtype mice and corticotropin releasing hormone-positive, but not vasopressin-positive, neurons within the PVN of wildtype and OT knockout mice. Fos expression was also increased following shaker stress in the bed nucleus of the stria terminalis, medial and central nuclei of the amygdala, medial preoptic area and the paraventricular nucleus of the thalamus of wildtype and OT knockout mice. However, Fos expression in the medial amygdala was significantly lower in female OT knockout mice than wildtype mice. Our findings indicate heightened stress-induced corticosterone release in female OT knockout mice. Therefore, the results suggest that OT pathways play a role in attenuating the HPA axis response to psychogenic stress in female mice.