HIV infection is linked to increased prevalence of depression which may affect maternal caregiving practices and place infants at increased risk of illness. We examined the incidence and days ill with diarrhea among infants of HIV positive (HIV-P), HIV negative (HIV-N), and unknown HIV status (HIV-U) women, and determined if symptoms of maternal postnatal depression (PND) modulated the risk of diarrhea. Pregnant women (n = 492) were recruited from three antenatal clinics; mothers and infants were followed for 12 months postpartum. Diarrheal incidence was 0.6 episodes/100 days at risk. More HIV-P than HIV-N and HIV-U women tended to report PND symptoms (χ(2) = 4.76; P = 0.09). Reporting symptoms was associated with an increased risk of infantile diarrhea only among HIV-P and HIV-U but not HIV-N women (interaction term, χ(2) = 7.84; P = 0.02). Health care providers should be aware of the increased risk of infantile diarrhea when both maternal HIV and PND symptoms are present and take preventive action.