PURPOSE: Our aim was to investigate the factors associated with mother-child separation at discharge, after joint hospitalization in psychiatric mother-baby units (MBUs) in France and Belgium. Because parents with postpartum psychiatric disorders are at risk of disturbed parent-infant interactions, their infants have an increased risk of an unstable early foundation. They may be particularly vulnerable to environmental stress and have a higher risk of developing some psychiatric disorders in adulthood. METHODS: This prospective longitudinal study of 1,018 women with postpartum psychiatric disorders, jointly admitted with their infant to 16 French and Belgian psychiatric mother-baby units (MBUs), used multifactorial logistic regression models to assess the risk factors for mother-child separation at discharge from MBUs. Those factors include some infant characteristics associated with personal vulnerability, parents' pathology and psychosocial context. RESULTS: Most children were discharged with their mothers, but 151 (15 %) were separated from their mothers at discharge. Risk factors independently associated with separation were: (1) neonatal or infant medical problems or complications; (2) maternal psychiatric disorder; (3) paternal psychiatric disorder; (4) maternal lack of good relationship with others; (5) mother receipt of disability benefits; (6) low social class. CONCLUSIONS: This study highlights the existence of factors other than maternal pathology that lead to decisions to separate mother and child for the child's protection in a population of mentally ill mothers jointly hospitalized with the baby in the postpartum period.