The aim of this research was to estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous adults in Australia’s most populous state, New South Wales (NSW). This was a prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009 and followed for hospitalisation for sepsis. We measured the incidence and hazard ratio (HR) of sepsis hospitalisation and ICU admission. Sepsis was identified using the International Classification of Diseases (10thRevision) coding on hospital discharge data. We found sepsis hospitalisation is higher among Aboriginal and Torres Strait Islander adults, but much of this excess risk attenuated after adjusting for sociodemographic risk factors. Culturally appropriate, community-led strategies targeting chronic disease prevention and the social determinants of health may reduce this gap.