BACKGROUND The aim of the study was to undertake a systematic review and meta-analysis of prospective studies to determine the effect of magnesium (Mg) supplementation on C-reactive protein (CRP). Design: Systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS Data sources: PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched (up until December 2016). Eligibility criteria: Randomized controlled trials evaluating the impact of Mg supplementation on CRP. We used random effects models meta-analysis for quantitative data synthesis. For sensitivity analysis was used the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Main outcome: Level of CRP after Mg supplementation. RESULTS From a total of 96 entries identified via searches, eight studies were included in the final selection. The meta-analysis indicated a significant reduction in serum CRP concentrations following Mg supplementation (weighted mean difference (WMD) -1.33 mg/l; 95% CI: -2.63 to -0.02, heterogeneity p < 0.123; I2 = 29.1%). The WMD for interleukin 6 was -0.16 pg/dl (95% CI: -3.52 to 3.26, heterogeneity p = 0.802; I2 = 2.3%), and 0.61 mg/dl (95% CI: -2.72 to 1.48, p = 0.182, heterogeneity p = 0.742; I2 = 6.1%) for fasting blood glucose. These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in serum CRP levels were independent of the dosage of Mg supplementation (slope: -0.004; 95% CI: -0.03, 0.02; p = 0.720) or duration of follow-up (slope: -0.06; 95% CI: -0.37, 0.24; p = 0.681). CONCLUSIONS This meta-analysis suggests that Mg supplementation significantly reduces serum CRP level. RCTs with a larger sample size and a longer follow-up period should be considered for future investigations to give an unequivocal answer.