We aimed to evaluate the National Early Warning Score-Lactate (NEWS-L) and NEWS to predict 24-hour mortality as the primary outcome. The secondary outcomes were to predict 48-hour, 28-day, and in-hospital mortality rates, and the need for critical care in patient with suspicion of sepsis at the emergency department (ED). Methods: A prospective observational study was performed in patients aged ≥18 years diagnosed with sepsis in the ED from March to November 2021. Area under the receiver operating characteristic curve (AUROC) analyses determined the predictive values of NEWS and NEWS-L for 24-hour mortality. Results: Ninety-two patients were enrolled (mean age 68 years, 48 [52.2%] males). Three (3.2%) patients died within 24 hours and 34 (36.9%) patients needed critical care during the ED stay. The median (interquartile range) NEWS and NEWS-L results were higher in the 24-hour non-survivors versus survivors: 12 (10.5, 12.5) versus 8 (6, 9) (p = 0.024) and 18.7 (15.2, 19.1) versus 10.6 (8.9, 13) (p = 0.036), respectively. The adjusted odds ratio (aOR) was 1.22 for the primary outcome as the NEWS-L increased by 1 unit without statistical significance (p = 0.228). The aOR values for the secondary outcomes ranged from 1.34 to 1.67 with statistical significance. A NEWS-L of 11 and a NEWS of 12 predicted 24-hour mortality with sensitivities/specificities of 100%/56% and 67%/91%, respectively. The AUROC values of NEWS-L for mortality at 24 hours, 48 hours, 28 days, and in-hospital patients, and the need for critical care were 0.860, 0.905, 0.813, 0.839, and 0.837, respectively. Conclusion: NEWS-L is an accurate predictor for 24-hour mortality in septic patients in the ED. NEWS-L performed better than NEWS for each outcome. NEWS-L demonstrated good to excellent performance and was accurate in predicting sepsis related to adverse outcomes.