In low-income countries, perinatal depression is common, but longitudinal data on its influence on child health are rare. We examined the association between maternal depression and febrile illness in children. There were 654 mother/child dyads in Ghana and Côte d'Ivoire that were enrolled in a prospective birth cohort in 2010-2011 and underwent 2-years of follow up. Mothers were examined for depression using the Patient Health Questionnaire depression module antepartum and 3 and 12 months postpartum. The hazard of febrile illness in children of depressed and nondepressed mothers was estimated using a recurrent event Cox proportional hazards model. The prevalences of antepartum depression in mothers from Côte d'Ivoire and Ghana were 28.3% and 26.3%, respectively. The prevalences of depression at 3 and 12 months postpartum were 11.8% and 16.1% (Côte d'Ivoire) and 8.9% and 7.2% (Ghana). The crude and adjusted (for country and socioeconomic status) hazard ratios of febrile illness in children of depressed mothers compared with those in children of nondepressed mothers were 1.57 (95% confidence interval: 1.20, 2.07) and 1.32 (95% confidence interval: 1.01, 1.74) respectively. Perinatal depression was frequent and associated with febrile illness in the offspring. Our results showed that a high prevalence of depression in sub-Saharan Africa may pose a serious public health threat to women and their offspring.