© 2020, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.Background: The benefit of end-tidal carbon dioxide (ETCO2) and inferior vena cava collapsibility index (IVCCI) in predicting fluid responsiveness in mechanically ventilated patients has been demonstrated. However, the data on spontaneously breathing patients is controversial. This study aims to investigate the accuracy of variations in the ETCO2 (∆ETCO2) and IVCCI (∆IVCCI) gradient in predicting volume responsiveness in spontaneously breathing patients with hypovolemia. Methods: This was a prospective observational study conducted in an academic emergency department (ED). Spontaneously breathing patients who required fluid resuscitation due to hypovolemia were included in the study. Cardiac output (CO), IVCCI and ETCO2 were measured before and after the passive leg raise (PRL). A change in the CO of ≥15% after the PLR were considered volume responsive. The difference in the ∆ETCO2 and ∆IVCCI were compared between the volume responsive and nonresponsive groups. Results: A total of 31 patients were included in the study, of whom 15 patients were volume responsive. The difference in the ∆ETCO2 was 4 mm Hg in the volume responsive and 2 mm Hg in the nonresponsive group (p = 0.02). There was no significant difference in ∆IVCCI between the groups. A moderate correlation was detected between the difference in ∆ETCO2 and CO (0.585; p = 0.001). Conclusion: ∆ETCO2 can be an alternative method in predicting volume responsiveness in spontaneously breathing patients with hypovolemia.