Because obesity is a common cause of obstructive sleep apnea syndrome (OSAS), weight loss can be an effective treatment. OSAS also may cause weight gain in some patients. Effective treatment of sleep apnea may facilitate weight loss in obese patients. We hypothesize that positive airway pressure (PAP) therapy is associated with weight loss in obese patients with OSAS. This was a single-center observational prospective cohort study. Forty-five patients were diagnosed with OSAS after polysomnographic analysis in sleep laboratory and underwent continuous positive airway pressure titration. Patients were followed for 3 months in terms of change in body mass index (BMI) and compliance with PAP therapy. Of the 45 patients recruited, 3 patients were eliminated because of miss recruitment. Nine patients had incomplete data, and the rest (n = 33) were included for analysis. The mean age was 54.9 ± 16.9 years (mean ± SD), 93.9% were male, and 90.9% were whites. Mean apnea-hypopnea index was 36.3 ± 28.17 events per hour. Mean BMI before treatment was 34.7 ± 3.9 kg/m. Fifteen patients (45.5%) were compliant with therapy of OSAS with PAP. There was no difference in age, gender, neck circumference, BMI, and apnea-hypopnea index of patients compliant to therapy when compared with those who were not. There was a significant decrease in BMI in patients compliant with PAP therapy compared with noncompliant patients (-1.2 ± 0.7 vs. 0.3 ± 0.9 kg/m, P ≤ 0.001). PAP therapy may cause significant loss of weight within 3 months in obese patients with OSAS. Further study is needed to elucidate the physiological basis of this change.