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Summary Background Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) and has been reported to be associated with chronic kidney disease (CKD). Recent studies have demonstrated that cystatin C is a prognostic biomarker of the risk of death and CVD even in patients without established CKD. Methods In a cross-sectional study, we enrolled 267 consecutive OSA patients without CKD who had an apnea-hypopnea index (AHI) ≥ 5 events per hour in overnight polysomnography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 according to the modification of diet in renal disease (MDRD) equation (modified for Japanese). Serum cystatin C levels were measured in all patients. Results Cystatin C was significantly correlated with age ( r = 0.37), body mass index (BMI) ( r = 0.12), AHI ( r = 0.17), C-reactive protein (CRP) ( r = 0.12), and Brachial-ankle pulse wave velocity ( r = 0.18). Logistic regression analysis demonstrated that severe OSA defined by an AHI ≥ 30 events per hour was an independent variable for the highest quartiles of serum cystatin C levels (≥0.88 mg/L) (OR: 2.04, 95% CI: 1.04–4.01, P = 0.04) even after adjustment for age, BMI ≥ 25, hypertension, and diabetes mellitus. Conclusions This study indicates that severe OSA independently increases serum cystatin C levels in patients without CKD. Cystatin C is considered to be a biomarker that reflects both clinically latent renal dysfunction and cardiovascular risk that are influenced by OSA.