PURPOSE Document risk factors for depressive symptoms during the postpartum period among working mothers, and determine longitudinal effects of depressive symptoms on maternal health-related quality of life and infant health and development. METHODS Mother-infant dyads from a community-based cohort study of working mothers were recruited when infants were four months old and interviewed every four months until infants were 16 months. Depressive symptoms and health-related quality of life were assessed using the Center for Epidemiologic Studies Depression Scale and the Short Form-12 Health Survey, respectively. Infant development and health-related quality of life were measured with the Ages and Stages Questionnaire and the Infant-Toddler Quality of Life Questionnaire, respectively. RESULTS Depressive symptoms were elevated among mothers who were younger, less educated, African American, unmarried, and impoverished. Mothers with significant depressive symptoms had significantly poorer physical and mental health-related quality of life, reported greater pain for their infant, and had more health-related concerns about their child. Maternal depressive symptoms at four months predicted infant poorer health-related quality of life at 8, 12 and 16 months.. CONCLUSIONS Several characteristics including age, education level, race, marital status, and poverty can help primary care physicians identify working mothers at risk for depressive symptoms. Identification of these symptoms is important; they are correlated with poorer maternal health-related quality of life and they predict poorer children’s health-related quality of life.