Our findings did not support the overall favorable effect of whey protein on circulating CRP level, based on the current evidence. However, the supplementation of whey protein and its derivates may produce a significant reduction in CRP among participants supplemented with a high dose of whey proteins or increased baseline CRP level. Although we successfully identified baseline CRP concentration as a potential effect modifier and major contributor to the overall between-study variation in meta-regression analysis, our results should be interpreted with caution because of the evidence of heterogeneity.