BackgroundInternational Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease.AimTo describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome.MethodsSecondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals.ResultsWe analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57–63) for sepsis; 35% (95%-CI 31–39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61–69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37–50). Agreement of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p< 0.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7–13.5) and 21.0 per 100,000 children (95%-CI 19.8–22.2) using validated study data.ConclusionsIn this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s44253-023-00006-1.