The aim of the current study was to compare the changes in polysomnographic indices and serum levels of C-reactive protein (CRP), cystatin C, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in patients with obstructive sleep apnea (OSA) who were treated surgically via a uvulopalatal flap (UPF) technique. Twenty-five patients (14 men, 11 women), average age 46.2 ± 9.3 years, who underwent UPF surgery were included in this study. Serum biochemical analyses and polysomnographic examinations were performed before and 6 months after the surgery. Pre- and postoperative values of apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum oxygen concentrations, as well as serum levels of CRP, cystatin C, TNF-α, and ICAM-1 were compared. Comparison of variables before and after UPF surgery demonstrated that AHI (p = 0.001), ODI (p < 0.001) and oxygen saturation (p < 0.001) were significantly improved. In addition, serum levels of CRP (p = 0.036), cystatin C (p = 0.005), TNF-α (p < 0.001), and ICAM-1 (p < 0.001) were significantly reduced 6 months after surgery. Our results suggest that UPF is an effective surgical method that alleviates the severity of OSA. Moreover, it may have the potential to prevent the development of atherosclerosis by attenuating the inflammatory process induced by activation of inflammatory mediators such as CRP, TNF-α, ICAM-1, and cystatin C.