Background/aim: Obstructive sleep apnea (OSA) is associated with serious cardiometabolic risks. Early diagnosis and treatment compliance are important. For this purpose, research is being carried out on biomarkers associated with the pathogenesis of the disease. We aimed to investigate whether serum S100A12 and S100B proteins could be used as biochemical markers in OSA patients to determine disease presence and severity. Materials and methods: A total of 60 (16 women, 44 men) patients with OSA and 50 (20 women, 30 men) controls were enrolled in this cross-sectional study. Each subject included in the study underwent full-night polysomnography (PSG). The presence and severity of OSA was assessed with the apnea-hypopnea index (AHI). In the OSA group, 17 cases were mild, 18 were moderate, and 25 were severe.The serum levels of S100A12 and S100B were measured using the enzyme-linked immunosorbent assay (ELISA) technique. These protein levels were compared using Student's t-test in the patient and control groups. Spearman's rho correlation coefficients and corresponding P-values were calculated to determine the correlations between these protein levels and polysomnographic parameters. For evaluating the association between OSA and biomarkers, as well as possible confounding factors with S100A12 and S100B, we employed multiple linear regression analyses for the patients with OSA.Results: Serum levels of S100A12 and S100B were higher in patients than those in controls (P = 0.01 and P = 0.005, respectively), and a significant correlation was determined between S100A12 and S100B values and AHI (P = 0.0001; P = 0.0001), sleep time with SpO2