IMPORTANCE: Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data. OBJECTIVE: To describe sepsis epidemiology in adults. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019. MAIN OUTCOMES AND MEASURES: The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed. RESULTS: Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality. CONCLUSIONS AND RELEVANCE: Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.