Patients suffering from both sleep apnea-hypopnea syndrome (SAHS) and chronic obstructive pulmonary disease (COPD) have a more severe form of sleep apnea. Knowing all pathophysiological aspects that mutually interact in sleep disorders and COPD, we aimed to investigate if the introduction of long-acting β2 agonists (LABA) during the night could improve overnight oxygenation and the ability to perform daily activities in stage I COPD patients with mild SAHS. We conducted a prospective study of 22 patients with stage I COPD and SAHS confirmed by overnight polygraph screening, without nocturnal CPAP treatment. During twelve weeks, all patients used LABA (salmeterol 50 mcg) with a metered dose inhaler before bedtime. The levels of apnea hypopnea index, oxygen saturation, heart rate, and Epworth daytime sleepiness scale (ESS) were recorded before and after the treatment. There was a significant improvement of lowest and average overnight oxygenation compared to baseline (mean difference 2.1±0.42, p<0.0001; 1.7±0.3, p<0.0001, respectively). In addition, patients reported reduction in daytime sleepiness according to ESS (mean difference 1.23±0.51; p=0.03). Fewer patients exhibited tachycardia when on salmeterol (68 vs. 41%; p=0.01). Use of inhaled salmeterol improves overnight oxygenation in patients with stage I COPD and SAHS. Future prospective studies are warranted to confirm this potentially beneficial effect of long-acting β2 agonists.