Heart rate (HR) at rest is associated with adverse cardiovascular events; however, the biologic mechanism for the relation is unclear. We hypothesized a strong association between HR at rest and subclinical inflammation, given their common interrelation with the autonomic nervous system. HR at rest was recorded at baseline in the Multi-Ethnic Study of Atherosclerosis, a cohort of 4 racial or ethnic groups without cardiovascular disease at baseline and then divided into quintiles. Subclinical inflammation was measured using high-sensitivity C-reactive protein, interleukin-6, and fibrinogen. We used progressively adjusted regression models with terms for physical activity and atrioventricular nodal blocking agents in the fully adjusted models. We examined inflammatory markers as both continuous and categorical variables using the clinical cut point of ≥3 mg/L for high-sensitivity C-reactive protein and the upper quartiles of fibrinogen (≥389 mg/dl) and interleukin-6 (≥1.89 pg/ml). Participants had a mean age of 62 years (SD 9.7), mean resting heart rate of 63 beats/min (SD 9.6) and were 47% men. Increased HR at rest was significantly associated with higher levels of all 3 inflammatory markers in both continuous (p for trend <0.001) and categorical (p for trend <0.001) models. Results were similar among all 3 inflammatory markers, and there was no significant difference in the association among the 4 racial or ethnic groups. In conclusion, an increased HR at rest was associated with a higher level of inflammation among an ethnically diverse group of subjects without known cardiovascular disease.