The prevalence of metabolic syndrome (MetS) has increased globally and is associated with an increased risk of cardiovascular diseases that may be related to its association with inflammation. We have assessed whether the prevalence of the MetS correlates with a serum high-sensitivity C-reactive protein (hsCRP) concentration in a population-based sample of US men and women. Participants were selected from the US National Health and Nutrition Examination Survey from 2005 to 2010. Of the 17 689 participants analyzed, 8607 (48.3%) were men. The mean age was 45.8 years in the overall sample (between men and women P = .047). The prevalence of MetS, diabetes mellitus, and hypertension increased across quartiles for hsCRP (all P < .001). Moreover, we found that for the age-, race-, sex-, and smoking-adjusted logistic regression, with increasing hsCRP, the risk of having MetS increased with an odds ratio of 5.20 (95% confidence interval, 4.54-5.93, P < .001) when comparing the highest quartile of serum hsCRP with the lowest. This study provides further evidence for an association between MetS and subclinical inflammation.