Evidence on the efficacy ofNigella sativa supplementation is equivocal, thus the aim of this systematic review and meta-analysis of randomized clinical trials (RCTs) was to examine the effect of Nigella sativa (N. sativa) supplementation on plasma C-reactive protein (CRP) concentrations.PubMed, Scopus, ISI Web of Science, Cochrane library, and Google Scholar databases were searched (up to April 2019) to identify RCTs investigating the effects of N. sativa seed and seed oil supplementation on CRP. Weighted mean differences (WMD) was pooled using a random-effects model. Standard methods were also used for assessment of heterogeneity, sensitivity analysis, and publication bias.Eventually only five articles which reported data of interest entered for data analysis. The meta-analysis showed a significant reduction in serum CRP (WMD: -0.55 mg/L, 95% CI: -1.02, -0.08, P = 0.02), with significant heterogeneity between selected studies (I = 77.3%). Between-study heterogeneity disappeared following subgroup analysis, stratified by baseline BMI (≥30 kg/m: I = 2.8%). However, the effect of N. sativa seed and seed oil supplementation on CRP was only significant in studies that were conducted on participants with BMI ≥ 30 kg/m (WMD: -0.50 mg/L, 95% CI: -0.85, -0.15).This meta-analysis suggests thatN. sativa seed and seed oil supplementation can significantly reduce serum CRP level. However, RCTs with a larger sample size and longer follow-up periods should be conducted for future investigations to confirm the veracity of these results.