Circulating 25-hydroxy vitamin D (25(OH)D) is related to decreased rates of gastrointestinal and ear infections in school-age children. Vitamin D-binding protein (DBP) transports 25(OH)D and exerts immunological functions; however, it is unknown whether DBP is associated with infectious morbidity in children. We quantified plasma DBP concentrations in 540 school-age children at the time of recruitment into a cohort study in Bogotá, Colombia and obtained daily information on infectious morbidity symptoms and doctor visits during the school year. We compared the incidence rates of gastrointestinal and respiratory symptoms across quartiles of DBP concentration by estimating adjusted incidence rate ratios (IRRs) with 95% confidence interval (CI). We also estimated the per cent of the associations between DBP and morbidity that were mediated through 25(OH)D using a counterfactual frame. Mean ± s.d. DBP concentration was 2650 ± 1145 nmol/l. DBP was inversely associated with the rates of diarrhoea with vomiting (IRR for quartiles 2–4 vs. 1 = 0.48; 95% CI 0.25–0.92; P = 0.03) and earache/ear discharge with fever (IRR for quartiles 2–4 vs. 1 = 0.29; 95% CI 0.12–0.71; P = 0.006). The DBP–morbidity associations were not mediated through 25(OH)D. We conclude that plasma DBP predicts lower incidence of gastrointestinal and ear infections in school-age children independent of 25(OH)D.