BACKGROUND Postpartum psychosis is a life-threatening psychiatric emergency, which often occurs without significant premorbid symptoms. Although many studies have postulated an involvement of the immune and endocrine systems in the onset of postpartum psychosis, the specific aetiological factors have remained unknown. OBJECTIVE To examine the hypothesis that autoimmune thyroid dysfunction may be associated with the onset of postpartum psychosis. METHODS Thirty-one consecutive primiparous women with no prior psychiatric history were referred to our in-patient unit for postpartum psychosis. The control group (n = 117) comprised primiparous women with consecutive deliveries at a community practice. Blood samples were obtained from all participants at 4 weeks and 9 months postpartum. Thyroperoxidase antibody levels were quantified as immunological measures of autoimmune thyroid disease (AITD). Thyroid-stimulating hormone and free thyroxine levels were measured to assess clinical thyroid dysfunction. RESULTS At 4 weeks postpartum and prior to the initiation of mood stabiliser therapy, 19% of women with postpartum psychosis had AITD compared with only 5% in the control group. Women with both postpartum psychosis and AITD had a dramatically higher risk of progression to clinical thyroid dysfunction (67%) than control participants with AITD (20%). CONCLUSIONS Women with postpartum psychosis are at higher risk not only of AITD but also of clinical thyroid failure. These data implicate thyroid function as an important clinical outcome in patients with postpartum psychosis. Further, AITD represents a potentially strong aetiological factor for the development of postpartum psychosis. Therefore, screening for thyroperoxidase antibodies is warranted in patients with postpartum psychosis.