The ability of end-tidal carbon dioxide (ΔEtCO2) for predicting fluid responsiveness has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of ΔEtCO2 for predicting fluid responsiveness during the passive leg raising (PLR) test in patients with mechanical ventilation. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2021. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Q test and I statistics were used for study heterogeneity and publication bias was assessed by Deeks' funnel plot asymmetry test. We performed meta-regression analysis for heterogeneity exploration and sensitivity analysis for the publication bias. Overall, six studies including 298 patients were included in this review, of whom 149 (50%) were fluid responsive. The cutoff values of ΔEtCO2 in four studies was 5%, one was 5.8% and the other one was an absolute increase 2 mmHg. Heterogeneity between studies was assessed with an overall Q = 4.098, I  = 51%, and P = 0.064. The pooled sensitivity and specificity for the overall population were 0.79 (95% CI 0.72-0.85) and 0.90 (95% CI 0.77-0.96), respectively. The DOR was 35 (95% CI 12-107). The pooled AUROC was 0.81 (95% CI 0.77-0.84). On meta-regression analysis, the number of patients was sources of heterogeneity. The sensitivity analysis showed that the pooled DOR ranged from 21 to 140 and the pooled AUC ranged from 0.92 to 0.96 when one study was omitted. Though the limited number of studies included and study heterogeneity, our meta-analysis confirmed that the ΔEtCO2 performed moderately in predicting fluid responsiveness during the PLR test in patients with mechanical ventilation.