Obesity, a multifactorial disorder, has been associated with alterations in metal metabolismand epigenetic modifications. This pilot case–control study aimed to investigate serum cobalt concentrations and associated DNA methylation patterns in women with obesity. Serum cobalt levels were measured using inductively coupled plasma mass spectrometry (ICP-MS), revealing significantly higher cobalt concentrations in participants with normal weight than in participants with obesity. Additionally, DNA methylation analysis identified differentially methylated positions (DMPs) associated with cobalt exposure, and DMPs between groups highlighted hypomethylation in the top DMPs in individuals with obesity. Functional enrichment analysis of these DMPs unveiled potential pathways implicated in apoptosis, cancer, and metabolic signaling, warranting further investigation into the mechanistic links. This study provides preliminary insights into the interplay between cobalt exposure, DNA methylation, and potential implications for obesity management.