Background Hyaluronic acid (HA) has been found to be an important trigger of atherosclerosis. In this study, we investigate the possible association of serum HA with cardiovascular disease risk in a population of low/intermediate risk for cardiovascular events. Methods We enrolled 200 subjects with low/intermediate risk for developing cardiovascular disease. High specific C‐reactive protein (hsCRP) was used as an indicator of preclinical atherosclerosis. The Framingham score was used to calculate the cardiovascular risk. Results Participants with dyslipidemia had significantly higher levels of serum HA than those without dyslipidemia (t‐test, P = 0.05), higher levels of hsCRP (Kruskal–Wallis test, P = 0.04), and higher cardiovascular risk according to the Framingham score (Kruskal–Wallis test, P = 0.05). Serum HA concentration correlated significantly with the Framingham score for risk for coronary heart disease over the next 10 years (Spearman r = 0.152, P = 0.02). Diabetic volunteers had significantly higher HA than those without diabetes (t‐test, P = 0.02). Participants with metabolic syndrome had higher serum HA levels and higher hsCRP (Kruskal–Wallis test, P = 0.01) compared to volunteers without metabolic syndrome (t‐test, P = 0.03). Conclusions Serum HA should be explored as an early marker of atheromatosis and cardiovascular risk.