BackgroundMalawi's PMTCT Option B+ program has expanded the reach of ART services among pregnant and breastfeeding women, but retention in lifelong HIV care remains challenging. Given that depression can undermine retention, it is important to understand how depression changes over the perinatal period, varies across treatment and retention groups, and could be buffered by social support. MethodsData are from an observational study conducted among women enrolled in Malawi's PMTCT Option B+ program. We used multilevel generalized linear models to estimate the odds of probable depression by time, treatment and retention group, and social support. Probable depression was assessed with the Edinburgh Postnatal Depression Scale and Patient Health Questionnaire-9. ResultsOf 468 women, 15% reported probable depression at antenatal enrollment and prevalence differed across newly diagnosed individuals, second line therapy users, and previous defaulters (18%, 21%, 5%, p = 0.001). Odds of probable perinatal depression decreased over time (OR per month: 0.87, 95% CI: 0.82–0.92) but were higher among those newly diagnosed (OR: 3.25, 95% CI: 1.59–6.65) and on second line therapy (OR: 3.39, 95% CI: 1.44–7.99) as compared to previous defaulters. Odds of probable postpartum depression were lower for participants with high social support (OR: 0.19, 95% CI: 0.09–0.39). LimitationsLack of diagnostic psychiatric evaluation precludes actual diagnosis of depression. ConclusionsProbable depression varied across the perinatal period and across treatment and retention groups. Social support was protective for postpartum depression among all participants. Depression screening and provision of social support should be considered in PMTCT programs.