Serum carbohydrate antigen 125 (CA-125) is a marker of ovarian cancer and obesity that is related with an increased risk of ovarian cancer. Obesity is a key factor of metabolic syndrome. We evaluated the relationship between CA-125 concentration and metabolic syndrome. The data from subjects who had any cancer and chronic infection were excluded. The data of 12,196 healthy Korean women were analyzed. After CA-125 concentration was divided by quartiles, the prevalence of metabolic syndrome and its components were compared. The lowest quartile of CA-125 compared with the highest quartile showed elevated values of most of metabolic parameters. In addition, as the quartile of CA-125 increased, metabolic derangement decreased. Increased numbers of metabolic syndrome components showed an inverse association with CA-125 levels (P < 0.001). The odds ratio (OR) for the lowest CA-125 quartile vs the highest CA-125 quartile significantly increased in the presence of metabolic syndrome (OR = 1.202, 95% Confidence Interval [CI] 1.013-1.423), elevated triglyceride (OR = 1.381, 95% CI 1.167-1.633), and low high-density lipoprotein cholesterol (OR = 1.168, 95% CI 1.039-1.312). The presence of metabolic syndrome, elevated triglyceride, or low high-density lipoprotein cholesterol negatively correlates with CA-125 concentration.