Objectives This study aims to investigate whether combining scoring systems with monocyte distribution width (MDW) improves early sepsis detection in older adults in the emergency department (ED). Methods In this prospective observational study, we enrolled older adults aged ≥60 years who presented with confirmed infectious diseases to the ED. Three scoring systems—namely quick sepsis-related organ failure assessment (qSOFA), Modified Early Warning Score (MEWS), and National Early Warning Score (NEWS), and biomarkers including MDW, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), were assessed in the ED. Logistic regression models were used to construct sepsis prediction models. Results After propensity score matching, we included 522 and 2088 patients with and without sepsis in our analysis from January 1, 2020, to September 30, 2021. NEWS ≥5 and MEWS ≥3 exhibited a moderate-to-high sensitivity and a low specificity for sepsis, whereas qSOFA score ≥2 demonstrated a low sensitivity and a high specificity. When combined with biomarkers, the NEWS-based, the MEWS-based, and the qSOFA-based models exhibited improved diagnostic accuracy for sepsis detection without CRP inclusion (c-statistics=0.842, 0.842, and 0.826, respectively). Of the three models, MEWS ≥3 with white blood cell (WBC) count ≥11 × 10 9 /L, NLR ≥8, and MDW ≥20 demonstrated the highest diagnostic accuracy in all age subgroups (c-statistics=0.886, 0.825, and 0.822 in patients aged 60–74, 75–89, and 90–109 years, respectively). Conclusions Our novel scoring system combining MEWS with WBC, NLR, and MDW effectively detected sepsis in older adults.