ObjectivesThis study aimed to explore the role of CT in septic patients presenting to the emergency department (ED).Materials and methodsWe performed a retrospective secondary analysis of 192 septic patients from a prospective observational study, i.e., the “LIFE POC” study. Sepsis was diagnosed in accordance with the Sepsis-3 definition. Clinical and radiological data were collected from the hospital administration and radiological systems. Information on mortality and morbidity was collected. Time-to-CT between CT scan and sepsis diagnosis (ttCTsd) was calculated. Diagnostic accuracy was assessed with the final sepsis source as reference standard. The reference standard was established through the treating team of the patient based on all available clinical, imaging, and microbiological data.ResultsSixty-two of 192 patients underwent a CT examination for sepsis focus detection. The final septic source was identified by CT in 69.4% (n = 43). CT detected septic foci with 81.1% sensitivity (95% CI, 68.0–90.6%) and 55.6% specificity (95% CI, 21.2–86.3%). Patients with short versus long ttCTsd did not differ in terms of mortality (16.1%, n = 5 vs 9.7, n = 3; p = 0.449), length of hospital stay (median 16 d, IQR 9 d 12 h–23 d 18 h vs median 13 d, IQR 10 d 00 h–24 d 00 h; p = 0.863), or duration of intensive care (median 3d 12 h, IQR 2 d 6 h–7 d 18 h vs median 5d, IQR 2 d–11 d; p = 0.800).ConclusionsOur findings show a high sensitivity of CT in ED patients with sepsis, confirming its relevance in guiding treatment decisions. The low specificity suggests that a negative CT requires further ancillary diagnostic tests for focus detection. The timing of CT did not affect morbidity or mortality outcomes.Clinical relevance statementIn patients with sepsis who present to the ED, CT can be used to identify infectious foci on the basis of clinical suspicion, but should not be used as a rule-out test. Scientific evidence for the optimal timing of CT beyond clinical decision-making is currently missing, as potential mortality benefits are clouded by differences in clinical severity at the time of ED presentation.Key Points• In patients with sepsis who present to the ED, CT for focus identification has a high sensitivity and can thereby be valuable for patient management.• As the specificity is considerably lower, a thorough microbiological assessment is important in these cases.• The timing of CT did not affect morbidity and mortality outcomes in this study, which might be due to variability in clinical severity at the time of ED presentation.