ObjectiveWe aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk factors for intensive care unit (ICU) admission and mortality.MethodsWe conducted a retrospective study of youth aged 2 to 21 years using International Classification of Diseases (ICD) codes for SLE assigned during admission to a hospital participating in the Pediatric Health Information System, a database of United States children's hospitals, from 2009 to 2021. Generalized linear mixed effects models were used to identify risk factors for ICU admission and mortality among children hospitalized with infection.ResultsWe identified 8588 children with cSLE and ≥ 1 hospitalization. Among this cohort, there were 26,269 hospitalizations, of which 13% had codes for infections, a proportion that increased over time (P= 0.04). Bacterial pneumonia was the most common hospitalized infection. In-hospital mortality occurred in 0.4% (n = 103) of cSLE hospitalizations for any indication and 2% of hospitalizations for infection (n = 60). The highest mortality rates occurred withPneumocystis jiroveciipneumonia (21%) and other fungal infections (21%). Lupus nephritis (LN) and endstage renal disease (ESRD) were associated with increased odds of ICU admission (odds ratio [OR] 1.47 [95% CI 1.2-1.8] and OR 2.40 [95% CI 1.7-3.4]) among children admitted for serious infection. ESRD was associated with higher mortality (OR 2.34 [95% CI 1.1-4.9]).ConclusionHospitalizations with ICD codes for infection comprised a small proportion of cSLE admissions but accounted for the majority of mortality. The proportion of hospitalizations for infection increased over time. LN and ESRD were risk factors for poor outcomes.