ABSTRACT Each year in the US, over 70,000 children are hospitalized with sepsis. Of the nearly 90% of children who survive sepsis, many face physical, emotional, and cognitive morbidity following sepsis hospitalization. Indeed, recent work by the proposed project’s research team—including through support from PI Carlton’s NCATS KL2 award—demonstrated that 1 in 20 children who survive sepsis develop new chronic respiratory failure (defined as supplemental oxygen dependence and/or invasive or non-invasive ventilator dependence) within 6 months of discharge. This rate of new chronic respiratory failure was nearly 2.5 times higher than in matched, non- septic, critically ill children. The proposed project will bring novel data to address several important gaps in understanding in order to mitigate and prevent the development of new chronic respiratory failure after sepsis. Using national multi-payer data (commercial insurance & Medicaid), the research team will characterize the patterns of onset of new chronic respiratory failure after sepsis. Secondly, the team will identify potentially modifiable factors associated with onset of this new morbidity. Specific aims include: Aim 1: To test the extent to which new chronic respiratory failure develops in-hospital versus post-discharge among children who survive sepsis hospitalization. Aim 2: To establish the antecedent and sepsis-specific risk factors associated with the onset of new chronic respiratory failure following sepsis. No studies, to the team’s knowledge, have described the time of onset of chronic respiratory failure after sepsis (i.e., developed during sepsis hospitalization vs. after discharge), nor assessed the explanatory risk factors for its development. The team anticipates that findings from the proposed project will fill critical knowledge gaps about the epidemiology and risk factors for postsepsis chronic respiratory failure that are necessary to enhance recovery. This work will provide key preliminary data for an R01 addressing the prevention, treatment, and management of sepsis-associated chronic respiratory failure among children.