Sepsis is a disease with high mortality and morbidity despite advances in diagnostic procedures and therapeutic strategies. The aim of this study was to evaluate the profile and outcomes of community-onset sepsis. This retrospective, multicenter study included five 24-h health care units and was conducted from January 2018 to December 2021. Patients were diagnosed with sepsis or septic shock according to the Sepsis 3.0 criterion. A total of 2630 patients diagnosed as having sepsis (68.4%, 1800) or septic shock (31.6%, 830) in the 24-h health care unit were included; 43.76% of the patients were admitted to the intensive care unit, 12.2% died, 4.1% had sepsis and 30% had septic shock. The comorbidities that were independent predictors of septic shock were chronic kidney disease on dialysis (CKD-d), bone marrow transplantation and neoplasia. CKD and neoplasia were also independent predictors of mortality, with ORs of 2.00 (CI 1.10–3.68) p = 0.023 and 1.74 (CI 1.319–2.298) p =  < 0.0001, respectively. Mortality according to the focus of primary infection was as follows: pulmonary 40.1%; COVID-19 35.7%; abdominal 8.1% and urinary 6.2%. Mortality due to the COVID-19 outbreak had an OR of 4.94 (CI 3.08–8.13) p ≤ 0.0001. Even though community-onset sepsis can be potentially fatal, this study revealed that some comorbidities lead to an increased risk of septic shock (d-CKD and neoplasia) and mortality. COVID-19 infection as the primary focus was an independent predictor of mortality in patients with sepsis when compared to other foci.