Demographic and geographic trends in sepsis-related mortality with respiratory failure in the United States, 1999–2024

Sepsis accompanied by respiratory failure carries a substantial mortality risk; systematic assessments of long-term mortality trends and demographic and geographic disparities remain limited. This study analyzed mortality involving both sepsis and respiratory failure among US adults from 1999 to 2024. Using the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database, we included US residents aged ≥ 25 years whose death certificates recorded both an explicit sepsis code and a respiratory failure code in any cause-of-death position. Age-adjusted mortality rates (AAMRs) were used to describe the mortality burden, and annual percent changes (APCs) and average annual percent changes (AAPCs) were calculated using Joinpoint regression. Stratified analyses were conducted by sex, age, race/ethnicity, census region, urban–rural classification, and state. A total of 911,119 deaths involving both sepsis and respiratory failure were recorded from 1999 to 2024. Annual deaths increased from 13,192 to 58,708 (345.03%), while the AAMR rose from 7.45 (95% CI: 7.32–7.58) to 20.68 (95% CI: 20.51–20.85) per 100,000 population (AAPC, 4.30%; 95% CI: 3.53%–5.07%). The AAMR increased from 1999 to 2018, accelerated during 2018–2021, and declined during 2021–2024; both annual deaths and the AAMR peaked in 2021. In 2024, the AAMR was higher in males than in females (24.16 vs. 17.99), highest among non-Hispanic Black individuals (28.46), and highest in the South (22.92). Adults aged ≥ 65 years accounted for 76.9% of deaths in 2024, while adults aged 55–64 years had the largest relative increase in deaths (430.79%). In 2020, the AAMR was higher in nonmetropolitan than in metropolitan areas (28.11 vs. 24.82), with a faster long-term increase (AAPC, 8.24% vs. 5.36%). From 1999 to 2024, mortality involving both sepsis and respiratory failure increased substantially in the United States, with a pronounced surge during the COVID−19 pandemic and a subsequent decline. Higher burdens were observed among males, older adults, non-Hispanic Black individuals, residents of the South, and nonmetropolitan populations. Enhanced surveillance, vaccination and infection prevention, early intervention, and regional critical care resource allocation for these high-burden groups are warranted.