The preference for empiric antibiotic therapy with carbapenems over non-carbapenems in all extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) colonized patients with sepsis warrants further investigation from an ecologic perspective; even more so in the elderly (≥ 65 years) because the proportion of ESBL-E in adults increases with patients' age. In this retrospective observational study, enrolling 547 ESBL-E colonized elderly patients with community-onset sepsis, hospitalized at a single medical centre from 2011 to 2015, the positive predictive value of ESBL-E faecal colonization for ESBL-E aetiology of sepsis was significantly higher (66.1%) when sepsis originated from a urinary tract infection than from a respiratory tract infection (26.1%), other known origins (31.6%), or an unidentified origin (13.0%). Carbapenems were prescribed empirically in 145 patients (26.5%), and 402 received non-carbapenem antibiotics. Univariate analysis suggested a higher 30-day mortality in the non-carbapenem vs. carbapenem group. However, the estimated association was smaller and not significant (OR = 1.1, 95% CI, 0.6-1.9, P = 0.62) in the multiple regression analysis adjusted for age, sex, Charlson comorbidity index score, and severity, origin or aetiology of sepsis. Therefore, carbapenem-sparing empiric therapy seems appropriate for non-critically ill elderly ESBL-E carriers with community-onset sepsis, even more so when sepsis originates outside urinary tract.