Background: Obstructive sleep apnea (OSA) is a chronic, progressive disease that can cause cardiovascular complications and atherosclerosis. We evaluated the relationship between serum bilirubin levels and carotid intima-media thickness (cIMT), as a surrogate marker of subclinical atherosclerosis, in patients with OSA. Methods: We enrolled 84 consecutive patients with OSA. The patients underwent ultrasonography, polysomnogaphy, and echocardiography. Blood samples were obtained from all of the subjects, which were used for biochemical comparisons. The patients were divided into groups according to cIMT values (<0.9 vs. >0.9 mm). Results: The patient population consisted of 84 OSA patients (mean age: 54.2 + 8.0 years, 62.9% male). The OSA patients with cIMT >= 0.9 had significantly elevated high-sensitive C-reactive protein (hsCRP), Oxygen desaturation index, apnea-hypopnea index (AHI), and significantly lower total and indirect bilirubin levels. Multivariate regression analyses revealed that total bilirubin, hsCRP, and AHI were the independent predictors of subclinical atherosclerosis. There was a negative correlation between total bilirubin and cIMT. Conclusions: This study showed that high hsCRP and low serum total bilirubin levels could be paving the way for the development of subclinical atherosclerosis. Simple measures such as total bilirubin may provide predictive information regarding the risk of cardiovascular disease in patients with OSA.