BackgroundSince oxygen content and oxygen consumption typically remain unchanged within a short period, variation in central venous oxygen saturation (ΔScvO2) during fluid challenge can theoretically track the changes in cardiac output (CO). We conducted this meta-analysis to systematically assess the diagnostic performance of ΔScvO2during a fluid challenge for fluid responsiveness in mechanically ventilated patients receiving volume expansion.MethodsElectronic databases were systematically searched to identify relevant studies published before October 24, 2022. As the cutoff value of ΔScvO2was expected to vary across the included studies, we estimated the area under the hierarchical summary receiver operating characteristic curve (AUHSROC) as the primary measure of diagnostic accuracy. The optimal threshold of ΔScvO2and the corresponding 95% confidential interval (CI) were also estimated.ResultsThis meta-analysis included 5 observational studies comprising 240 participants, of whom 133 (55%) were fluid responders. Overall, the ΔScvO2during the fluid challenge exhibited excellent performance for defining fluid responsiveness in mechanically ventilated patients receiving volume expansion, with an AUHSROC of 0.86 (95% CI 0.83–0.89), a pooled sensitivity of 0.78 (95% CI 0.69–0.85), a pooled specificity of 0.84 (95% CI 0.72–0.91), and a pooled diagnostic odds ratio of 17.7 (95% CI 5.9–53.2). The distribution of the cutoff values was nearly conically symmetrical and concentered between 3 and 5%; the mean and median cutoff values were 4% (95% CI 3–5%) and 4% (95% CI not estimable), respectively.ConclusionsIn mechanically ventilated patients receiving volume expansion, the ΔScvO2 during the fluid challenge is a reliable indicator of fluid responsiveness.Clinical trial registrationPROSPERO,https://www.crd.york.ac.uk/prospero/, registry number: CRD42022370192.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13054-023-04480-z.