OBJECTIVES: In 2013, French (FR) and United States (US) hospitals managed an average of 152 and 316 sepsis hospitalizations annually per hospital. While no specific treatment can prevent all sepsis complications, early recognition and treatment is associated with reduced sepsis severity and mortality. This study estimates the benefits of reducing sepsis severity in France and the US. METHODS: A deterministic decision tree model was designed to counterfactually estimate the potential cost offsets of reducing sepsis severity. Model inputs included sepsis severity, mortality, length of stay, time in the ICU, and costs. Inputs were based on country-specific data for France and US using a focused literature review, PMSI data (France) and NIS (US) to inform population, clinical and economic variables. The current distribution of sepsis severity [sepsis (FR: 51%; US: 28%), severe sepsis (FR: 22%; US: 66%) and septic shock (FR: 27%, US: 6%)] is used to define the base case. To estimate the potential benefit of improving sepsis severity, the analysis simulated shifts in sepsis severity of 10%, 25%, and 50%, which results in a population shifting from higher (severe and septic shock) to lower levels of severity (sepsis). Analyses were conducted at the patient and hospital in 2017 currency. RESULTS: Reduction in sepsis severity resulted in substantial cost offsets. In FR, a 10%, 25% and 50% shift to lower sepsis severity levels resulted in annual savings per patient of €207 to €1,035 and per hospital of €31,480 to €157,399. In the US, a 10%, 25% and 50% shift to lower sepsis severity levels resulted in annual savings per patient of $593 to $2,967 and per hospital of $187,515 to $937,574. CONCLUSIONS: Innovations in sepsis diagnosis and management that reduce the severity of sepsis in French and US hospitals may offer significant economic value to hospitals managing sepsis populations.