High rates of depression associated with childbirth have been reported in many parts of the developing world. However, the prevalence and associations of antenatal and post-natal depression in the rural population remain unknown. Disability associated with depression and its impact on infant health and development could have important public health implications for many developing countries where large proportions of the population are rural. All women living in southern Kahuta, Pakistan, in their third trimester of pregnancy were interviewed at 6 weeks before delivery (N = 632) and again at 10-12 weeks after delivery (N = 541), using WHO Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Personal Information Questionnaire (PIQ) and Brief Disability Questionnaire (BDQ). The point prevalence of ICD-10 depressive disorder was 25% in the antenatal period and 28 % in the post-natal period. Depressed mothers were significantly more disabled, had more threatening life events, and poorer social and family support than non-depressed mothers. Vulnerable mothers were more likely to be depressed during pregnancy, rather than have an onset in the post-natal period. Over one-quarter of mothers in a rural sub-district of Pakistan suffer from depression shortly before and after childbirth. Rapidly changing traditional family structures and practices may be increasing the risk of depression in many women. Recognizing and treating depression should be initiated during the antenatal, rather than post-natal period.