Depression around childbirth is common in low income countries. The aim of this study was to examine the factors associated with persistence of depression from the antenatal to the postnatal period in urban Pakistan. A total of 1,357 pregnant women in their third trimester attending the antenatal clinic were included in the study. From these, 763 mothers who delivered at the study maternity home were reassessed after 3 months of childbirth. Edinburgh Postnatal Depression Scale (EPDS) was administered to measure depression in both the antenatal and the postnatal periods. Psychological distress, disability and life events experienced by mothers were also measured by using the Self-Reporting Questionnaire (SRQ-20), Brief Disability Questionnaire (BDQ), and Life Events Checklist, respectively. We found 25.8% prevalence rate of antenatal depression and 38.3% persistent depression in a private clinic. Persistently depressed mothers had significantly high psychological distress, more disability, and experienced more stressful life events than the resolved group. Our findings confirm the high rates of depression during pregnancy but we found low rates of persistent depression in this urban population as compared to the previous report. There is a need for further investigation of factors associated with persistent depression in order to develop appropriate interventions.