In many African countries, child mortality is higher in the rainy season than in the dry season. We investigated the effect of season on child mortality by time periods, sex and age in rural Guinea-Bissau. Bandim health project follows children under-five in a health and demographic surveillance system in rural Guinea-Bissau. We compared the mortality in the rainy season (June to November) between 1990 and 2013 with the mortality in the dry season (December to May) in Cox proportional hazards models providing rainy vs. dry season mortality rate ratios (r/d-mrr). Seasonal effects were estimated in strata defined by time periods with different frequency of vaccination campaigns, sex and age (<1 month, 1-11 months, 12-59 months). Verbal autopsies were interpreted using InterVa-4 software. From 1990 to 2013, overall mortality was declined by almost two-thirds among 81 292 children (10 588 deaths). Mortality was 51% (95% ci: 45-58%) higher in the rainy season than in the dry season throughout the study period. The seasonal difference increased significantly with age, the r/d-mrr being 0.94 (0.86-1.03) among neonates, 1.57 (1.46-1.69) in post-neonatal infants and 1.83 (1.72-1.95) in under-five children (P for same effect <0.001). According to the InterVa, malaria deaths were the main reason for the seasonal mortality difference, causing 50% of all deaths in the rainy season, but only if the InterVa included season of death, making the argument self-confirmatory. The mortality declined throughout the study, yet rainy season continued to be associated with 51% higher overall mortality.