Abstract Inflammation plays a critical role in the pathogenesis of obstructive sleep apnea syndrome (OSAS). YKL-40 is a novel biomarker of systemic inflammation. We aim to detect serum YKL-40 concentrations in OSAS patients and to clarify their relationship with clinical severity of the disease. We enrolled 159 OSAS patients and 104 healthy controls. The presence and severity of OSAS was assessed by Apnea-hypopnea index (AHI). Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA). We demonstrated that serum YKL-40 concentrations were significantly elevated in OSAS patients than those in controls. Multivariate logistic regression including all variables revealed that YKL-40 was the significant and independent predictor for the present of OSAS. In OSAS patients, there is a significant positive correlation between increments in serum YKL-40 concentrations and severity of OSAS. Serum YKL-40 concentrations were independently and significantly correlated with AHI scores. These results suggest that YKL-40 could be used as a potential biomarker for predicting the development and progression of OSAS.