Sepsis is a major cause of hospital admissions and mortality. Nevertheless, there are significant gaps in our knowledge of the epidemiology of sepsis in obese people, who now represent more than one-third of the population in the United States. The objective of this study was to measure the association between obesity and mortality from presumed sepsis. A retrospective cohort study was used of 1,779 adult inpatients with presumed sepsis at a Tertiary Care Academic Institution from March 1, 2007 to June 30, 2011. Cases of sepsis were identified using a standardized algorithm for sepsis antibiotic treatment. Exposure (i.e., obesity) was defined as a body mass index ≥30 kg/m(2). Multivariable logistic regression was used to assess the adjusted association between obesity and mortality. Patients with presumed sepsis were of a median age of 60.9 years (interquartile range 49.7-71) and 41.1 % were women. A total of 393 patients died, resulting in a 28-day in-hospital mortality of 22.1 %. In adjusted analysis, obesity was not significantly associated with increased mortality (odds ratio 1.11, 95 % CI 0.85-1.41, P = 0.47). There was also no difference in the in-hospital length of stay (P = 0.45) or maximum percent change in serum creatinine (P = 0.32) between obese and non-obese patients. Finally, there was no difference in the proportion of initial inadequate vancomycin levels (P = 0.1) after presumed sepsis. Obesity was not associated with increased mortality in patients with presumed sepsis. Further research is needed to determine how excess adiposity modulates inflammation from sepsis.