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Abstract Introduction: Disseminated intravascular coagulation (DIC) is a life-threatening coagulopathy frequently associated with sepsis, markedly increasing mortality over 30% to 50%. Recent studies suggested that coagulation disturbances contribute directly to sepsis-induced organ dysfunction. However, DIC-specific treatments remain limited, and current diagnostic approaches often detect DIC in its late stages. This delay underscores a critical gap in care and highlights the urgent need for early detection of DIC to improve survival outcomes in septic patients. The aim of our study is to explore public health initiatives and to inform specifically directed prevention and treatment strategies. Methods: The mortality trends among adults aged ≥25 with DIC and septicaemia were analyzed using data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) database, where DIC and Septicaemia ere presented as a contributing or the underlying cause of death. Code D65 “Disseminated intravascular coagulation” and Code A41.0 “Other Septicaemia” in the International Classification of Disease, tenth revision (ICD-10) were used to identify the data. Crude and age-adjusted mortality rates (AAMRs) per 100,000 people were extracted. Annual percent changes (APCs) in AAMRs with 95% CI were obtained through linear regression analysis across different demographic (sex, race/ethnicity, and age) and geographic (state, urban-rural, and regional) subgroups. Results: Between 1999 and 2020, 3,687,955 documented deaths were attributed due to DIC in adults with septicaemia. The overall AAMR for DIC and Septicaemia-related mortality decreased in the US from an adjusted rate (AR) 77.7 in 1999 to 72.8 in 2012 (APC: -0.34%; 95% CI: -1.69% to 0.15%), after which it increased to 90.7 in 2020 (APC: 1.78%; 95% CI: 0.80% to 5.13%). Males had consistently higher AAMRs than females (106.1 vs. 78.7). The AAMR in the US men decreased from 89.8 in 1999 to 82.8 in 2012 (APC: -0.50%; 95% CI: -1.80% to -0.13%) after which it increased to 106.1 in 2020 (APC: 2.14%; 95% CI: 1.06% to 5.54%). The AAMR in the US women decreased from 69.3 in 1999 to 65.6 in 2012 (APC: -0.29%; 95% CI: -2.32% to -0.28%) after which it increased to 78.7 in 2020 (APC: 1.36%; 95% CI: 0.48% to 4.64%). The non-Hispanic (NH) Black or African American (AA) population has the greatest AAMR (143.2), followed by the NH American Indian or Alaska Native with an AAMR (137.3) and the Hispanic or Latino population with an AAMR (100.3). The low-risk population was the NH White population (83.5) and the NH Asian or Pacific Islander (59.8). AAMR also varied by region (overall AAMR: South: 102.9; Midwest: 86.9; Northeast: 83.1; West: 79.7) and non-metropolitan areas had higher AAMR (non-core areas: 104.1; micropolitan areas: 101.4; small metro areas: 94.9) than metropolitan areas (large central metropolitan areas: 89.4; large fringe areas: 82.5). The states in the upper 90th percentile of DIC and septicaemia-related AAMRs were Oklahoma, Arkansas, Texas, Louisiana, Mississippi, Alabama, Tennessee, Kentucky, Georgia and South Carolina exhibited an approximately two-fold increase in AAMRs, compared to states falling in the lower 10th percentile Oregon, Idaho, Arizona, Colorado, Minnesota and Maine. Conclusions: The mortality rates from disseminated intravascular coagulation (DIC) in patients with septicaemia have overall increased in the United States over the past two decades. But NH Black or AA, NH American Indian or Alaska Native followed by Hispanic or Latino men, are at more risk than NH White and Asian or Pacific Islander.