Background Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of hypoxemia and hypercapnia during sleep. The aim of this study was to determine whether OSAS causes significant changes in corneal endothelium detectable by specular microscopy. Methods This prospective, cross-sectional study compared the specular microscopic features of the corneal endothelium of patients with OSAS and age-and gender-matched controls. Patients diagnosed with OSAS by polysomnography in the sleep unit were classified using apnea-hypopnea indexes into two groups as mild-moderate OSAS group and severe OSAS group. All participants were divided into three age groups: 30-45, 46-60, and > 60 years. Corneal endothelial cell density (ECD), percentage of hexagonal cells (Hex), and coefficient of variation of cell area (CV) were obtained using a non-contact specular microscope. The measurements of each group were compared statistically. Results A total of 66 patients (51.1 +/- 9.4 years) and 88 controls (49.2 +/- 10.5 years) were examined. The mild-moderate OSAS group and the severe OSAS group had no significant differences in measures of specular microscopy compared with the controls (ECD, p = 0.84; Hex, p = 0.18; CV, p = 0.41). The mean values of ECD, Hex, and CV were 2552.56 +/- 302.49 cells/mm(2), 54.13 +/- 8.13%, and 36.41 +/- 5.92, respectively, in the mild-moderate OSAS group; 2510.52 +/- 377.12 cells/mm(2), 54.85 +/- 8.68%, and 34.77 +/- 5.02, respectively, in the severe OSAS group; 2543.37 +/- 286.94 cells/mm(2), 51.89 +/- 9.09%, and 36.03 +/- 5.32, respectively, in the control group. Conclusions There were no significant differences in corneal endothelial features between patients and controls. Although OSAS causes systemic hypoxia, its effects do not appear to result in corneal endothelial alterations detectable by specular microscopy.