Background:Identifying DNA methylation sites that regulate the metabolome is important for several purposes. In this study, publicly available GWAS data were integrated to find methylation sites that impact metabolome through a discovery and replication scheme and by using Mendelian randomization.Results:The outcome of analyses revealed 107 methylation sites associated with 84 metabolites at the genome-wide significance level (p<5e−8) at both the discovery and replication stages. A large percentage of the observed associations (85%) were with lipids, significantly higher than expected (p= 0.0003). A number of CpG (methylation) sites showed specificity e.g., cg20133200 withinPFKPwas associated with glucose only and cg10760299 withinGATMimpacted the level of creatinine; in contrast, there were sites associated with numerous metabolites e.g., cg20102877 on the 2p23.3 region was associated with 39 metabolites. Integrating transcriptome data enabled identifying genes (N = 82) mediating the impact of methylation sites on the metabolome and cardiometabolic traits. For example,PABPC4mediated the impact of cg15123755-HDL on type-2 diabetes.KCNK7mediated the impact of cg21033440-lipids on hypertension.POC5, ILRUN, FDFT1,andNEIL2mediated the impact of CpG sites on obesity through metabolic pathways.Conclusion:This study provides a catalog of DNA methylation sites that regulate the metabolome for downstream applications.