Objective: Troponin I is a cardiac biomarker to diagnose acute myocardial infarction and is known to be elevated in sepsis patients as well. Recent studies have shown a correlation between troponin I results the prognosis of sepsis patients. We attempted to correlate the serial measurements of high-sensitivity troponin I (Hs-TnI) results with the prognosis of sepsis patients visiting the emergency room (ER). Methods: We conducted a retrospective study of patients who visited the ER from December 2019 to May 2021 with a diagnosis of infectious disease and a quick Sequential Organ Failure Assessment (qSOFA) score of over two. Those who had been administered the 3-hour interval Hs-TnI test were selected and the difference between two Hs-TnI (delta Hs-TnI) results were correlated with the prognosis of the patient. Results: A total of 76 patients were included in the study, including 56 28-day survivors and 20 28-day non-survivors. The delta Hs-TnI was higher in the non-survivor group and associated with a poorer prognosis (P=0.004). Multivariate logistic regression was used, and log(delta Hs-TnI) showed an odds ratio (OR) of 2.227 (95% confidence interval [CI], 1.171-5.818), (P=0.023) while the Sequential Organ Failure Assessment (SOFA) score showed an OR of 1.478 (95% CI, 1.229-1.777) (P<0.001). The area under the curve (AUC) was calculated using the receiver operating characteristic curve and the AUC for the SOFA score was 0.893 and that from the log(delta Hs-TnI) was 0.724. Conclusion An increase in delta Hs-TnI is correlated with the poorer prognosis of sepsis patients. Hence, it would be useful to check the serial Hs-TnI to predict the 28-day outcome of sepsis patients visiting the ER.