Purpose: There are conflicting data regarding the role of the National Early Warning Score 2 (NEWS2) in predicting adverse outcomes in patients with infectious diseases. New-onset atrial fibrillation (NO-AF) has been suggested as a sepsis-defining sign of organ dysfunction. This study aimed to examine the prognostic accuracy of NEWS2 and whether NO-AF can provide prognostic information in emergency department (ED) patients with suspected bacterial infections. Patients and Methods: Secondary analyses of data from a prospective observational cohort study of adults admitted in a 6-month period with suspected bacterial infections. We used the composite endpoint of in-hospital mortality or transfer to the intensive care unit as the primary outcome. The prognostic accuracy of NEWS2 and quick sequential organ failure assessment (qSOFA) and covariate-adjusted area under the receiver operating curves (AAUROC) were used to describe the performance of the scores. Logistic regression analysis was used to examine the association between NO-AF and the composite endpoint. Results: A total of 2055 patients were included in this study. The composite endpoint was achieved in 198 (9.6%) patients. NO-AF was observed in 80 (3.9%) patients. The sensitivity and specificity for NEWS2 ≥5 were 70.2% (63.3–76.5) and 60.2% (57.9–62.4), respectively, and those for qSOFA ≥2 were 26.3% (20.3–33.0) and 91.0% (89.6–92.3), respectively. AAUROC for NEWS2 and qSOFA were 0.68 (0.65–0.73) and 0.63 (0.59–0.68), respectively. The adjusted odds ratio for achieving the composite endpoint in 48 patients with NO-AF who fulfilled the NEWS2 ≥5 criteria was 2.71 (1.35–5.44). Conclusion: NEWS2 had higher sensitivity but lower specificity and better, albeit poor, discriminative ability to predict the composite endpoint compared to qSOFA. NO-AF can provide important prognostic information.