In low- and middle-income countries, perinatal depression (PND) has been associated with poor infant health outcomes, including frequency of infant diarrheal episodes, preterm delivery and low birth weight, and discontinuation or problems breastfeeding. Yet little is known about the awareness or expression of PND depression in Ghana. A total of 12 in-depth key-informant interviews were conducted with women who had experienced PND within the previous two-and-a-half years. Three focus-group discussions were conducted with new mothers (n = 11), grandmothers (n = 8), and fathers (n = 9) for contextual and supporting information. ‘Thinking too much’ was the term most commonly used to describe PND. The women saw their distress as caused largely by poverty, lack of social support, and domestic problems. Women sought help through family and religious organizations, rather than through medical services. Problems producing breast milk or breastfeeding were nearly universal complaints and suggest significant effects on infant health in the study area. These results present evidence to support the increasing consensus that depression presents in similar and disabling ways across cultures and contexts. This formative qualitative data is required to tailor depression prevention or treatment interventions to this particular socio-cultural context.