Background. Postnatal depression (PND) is one of the most common complications following delivery. The development of PND is closely linked with biological, psychological, socioeconomic and cultural factors. Objectives. To determine the prevalence and identify risk factors for PND in mothers delivering at Steve Biko Academic Hospital (SBAH) whose babies were admitted to the neonatal unit. Methods. We conducted a prospective observational study at SBAH, Pretoria, South Africa (SA). Women who delivered between 26 and 42 weeks' gestation at SBAH and whose babies were admitted to the neonatal unit were recruited at delivery. Interview screening using the Edinburgh Postnatal Depression Scale (EPDS) was conducted regarding the mother's experience of her pregnancy and delivery. Sociodemographic and psychosocial data from the mothers were included in a multiple logistic regression model to estimate association with PND symptoms. Results. Between 11 March and 30 December 2017, 2 671 mothers delivered at SBAH. Of these, 196 (7.3%) babies were admitted to the neonatal intensive care unit (NICU) and 10 (0.3%) were admitted to the neonatal high care unit (NHC). Mothers' accommodation during their babies' admission to the neonatal unit (p=0.002), having poor interpersonal relationships (p<0.0001), and intimate partner violence (IPV) (p=0.004) were significantly associated with screening positive for PND. Conclusion. Accommodation during neonatal care, availability of counselling, inclusion of the partner in postnatal care and IPV are significant factors in the depressive symptoms experienced by mothers postpartum in this setting.