Promising experimental studies suggest that quercetin has potential anti-inflammatory effects. However, the results of current clinical trials on quercetin's effects on the C-reactive protein (CRP), a sensitive inflammatory biomarker, are ambiguous. We conducted a meta-analysis of available randomized controlled trials (RCTs) to resolve this inconsistency and quantify the net effect of quercetin on circulating CRP concentrations. A systematic search was performed in several databases including SCOPUS, PubMed-Medline and Google Scholar until 16 June 2016. We used a random-effects model in combination with weight mean difference (WMD) and 95% confidence intervals (CI) for data analysis. Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias. The meta-analysis of seven RCTs (10 treatment arms) showed a significant reduction of circulating CRP levels (WMD: - 0.33 mg/l; 95% CI: - 0.50 to - 0.15; P < 0.001) following quercetin supplementation. In the subgroup analysis, a significant reducing effect was observed in trials with ≥ 500 mg/day dosage (WMD: - 0.34 mg/l; 95% CI: - 0.52, - 0.16; P ≤ 0.001) and in those with CRP < 3 mg/l (WMD: - 0.34 mg/l; 95% CI: - 0.51, - 0.18; P ≤ 0.001). In meta-regression, there was no association between changes in CRP concentrations, dose of supplementation and CRP baseline values. Our findings showed a significant effect of quercetin supplementation on the C-reactive protein—especially at doses above 500 mg/day and in patients with CRP < 3 mg/l.