Objective: Leptin hormone plays an important role in metabolic control and is elevated in obstructive sleep apnea (OSA). The aim of this study was to assess the hypothesis that surgical treatment will reduce leptin levels in OSA patients. Study Design: Prospective study. Subjects and Methods: Twenty-three patients with multilevel OSA underwent modified genioglossus muscle advancement with anterolateral advancement pharyngoplasty between April 2018 and September 2019. Serum leptin level was measured preoperatively and 3 months postoperatively for all patients and 18 control subjects. All patients were evaluated before and 3 months after surgery by history taking, clinical examination, polysomnography, cephalometry, and Epworth Sleepiness Scale. Results: Preoperatively, patients with OSA had a higher Leptin level (18.46 ± 4.73 ng/mL) than did control subjects (7.07 ± 1.26 ng/mL) (P < .001). Surgery resulted in a significant reduction in the level of leptin from 18.46 ± 4.73 ng/mL to 8.03 ± 2.22 ng/mL (P < .001). Reductions in leptin level was correlated with changes in apnea hypopnea index (AHI) (r = 0.61, P = .002) and minimum oxygen saturation (SaO2) (r = −0.54, P = .008). Conclusion: Effective multilevel surgery in the form of modified genioglossus muscle advancement with anterolateral advancement pharyngoplasty could significantly reduce leptin level in OSA patients and this reduction is correlated with the degree of OSA improvement in term of AHI and SaO2.