Abstract / Summary
Abstract Background Sepsis and obesity are each major public health burdens in the United States, and their co-occurrence has not previously been characterized using multiple-cause-of-death (MCD) surveillance, which captures conditions recorded anywhere on the death certificate rather than only the underlying cause. We examined long-term national trends and disparities in mortality involving co-documented sepsis and obesity. Methods In this retrospective serial cross-sectional study, we used Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) multiple-cause-of-death data to identify United States deaths among adults aged 25 years or older, from 1999 through 2024, in which sepsis and obesity were both recorded anywhere on the death certificate. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated overall and by sex, Hispanic origin, race and ethnicity, census region, urbanization, and state. Temporal trends were assessed using Joinpoint regression, with annual percentage change and average annual percentage change estimated for each identified trend segment. Results From 1999 through 2024, 64,163 deaths involved co-documented sepsis and obesity. The overall AAMR rose from 0.41 (95% CI, 0.38–0.44) per 100,000 in 1999 to a peak of 2.95 (95% CI, 2.88–3.02) in 2021, then declined to 1.46 (95% CI, 1.42–1.51) in 2024, tracing a steady rise (1999–2018), a sharp pandemic-era acceleration (2018–2021), and a partial reversal (2021–2024). Mortality was consistently higher among women, non-Hispanic American Indian/Alaska Native and Native Hawaiian/Pacific Islander decedents, and residents of the South and nonmetropolitan counties, with the highest state-level burden in Oklahoma. Conclusions Mortality involving co-documented sepsis and obesity rose substantially in the United States over 25 years, driven by a pandemic-era surge that has only partially reversed, and disproportionately burdened women, American Indian/Alaska Native, Native Hawaiian/Pacific Islander, and Black populations, and residents of the South and rural America. These findings support continued multiple-cause-of-death surveillance and identify actionable public health and policy priorities: targeted expansion of rural and equity-focused sepsis-care quality improvement, and integration of obesity prevention into infection-mortality prevention strategy. Clinical trial number: not applicable.