Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. The risk of PP is very high in women with a history of bipolar affective disorder or schizoaffective disorder. However, the neurobiological basis of PP remains poorly understood and no study has evaluated brain structure in women at risk of, or with, PP. We performed a cross-sectional study of 256 women at risk of PP and 21 healthy controls (HC) in the same postpartum period. Among women at risk, 11 who developed a recent episode of PP (PPE) (n = 2 with lifetime bipolar disorder; n = 9 psychotic disorder not otherwise specified) and 15 at risk women who did not develop an episode of PP (NPPE) (n = 10 with lifetime bipolar disorder; n = 1 with schizoaffective disorder; n = 1 with a history of PP in first-degree family member; n = 3 with previous PP). We obtained T1-weighted MRI scans at 3T and examined regional gray matter volumes with voxel-based morphometry and cortical thickness and surface area with Freesurfer. Women with PPE showed smaller anterior cingulate gyrus, superior temporal gyrus and parahippocampal gyrus compared to NPPE women. These regions also showed decreased surface area. Moreover, the NPPE group showed a larger superior and inferior frontal gyrus volume than the HC. These results should be interpreted with caution, as there were between-group differences in terms of duration of illness and interval between delivery and MRI acquisition. Nevertheless, these are the first findings to suggest that MRI can provide information on brain morphology that characterize those women at risk of PP more likely to develop an episode after childbirth.