A quick, objective, non-invasive means of identifying high-risk septic patients in the emergency department (ED) can improve hospital outcomes through early, appropriate management. Heart rate variability (HRV) analysis has been correlated with mortality in critically ill patients. We aimed to develop a Singapore ED sepsis (SEDS) predictive model to assess the risk of 30-day in-hospital mortality in septic patients presenting to the ED. We used demographics, vital signs, and HRV parameters in model building and compared it with the modified early warning score (MEWS), national early warning score (NEWS), and quick sequential organ failure assessment (qSOFA) score. Adult patients clinically suspected to have sepsis in the ED and who met the systemic inflammatory response syndrome (SIRS) criteria were included. Routine triage electrocardiogram segments were used to obtain HRV variables. The primary endpoint was 30-day in-hospital mortality. Multivariate logistic regression was used to derive the SEDS model. MEWS, NEWS, and qSOFA (initial and worst measurements) scores were computed. Receiver operating characteristic (ROC) analysis was used to evaluate their predictive performances. Of the 214 patients included in this study, 40 (18.7%) met the primary endpoint. The SEDS model comprises of 5 components (age, respiratory rate, systolic blood pressure, mean RR interval, and detrended fluctuation analysis alpha 2) and performed with an area under the ROC curve (AUC) of 0.78 (95% confidence interval [CI]: 0.72-0.86), compared with 0.65 (95% CI: 0.56-0.74), 0.70 (95% CI: 0.61-0.79), 0.70 (95% CI: 0.62-0.79), 0.56 (95% CI: 0.46-0.66) by qSOFA (initial), qSOFA (worst), NEWS, and MEWS, respectively. HRV analysis is a useful component in mortality risk prediction for septic patients presenting to the ED.