Abstract Aim: to evaluate the acute effects of expiratory positive airway pressure on cardiac autonomic modulation in chronic obstructive pulmonary disease patients during spontaneous breathing and slow deep breathing. Methods: 17 patients were evaluated. The R-R intervals were collected (Polar® S810i) during spontaneous breathing (10 minutes) and slow deep breathing (4 minutes), with and without 5 cmH2O expiratory positive airway pressure. Stable signals were analyzed by Kubios®. Heart rate variability indices were computed in time domain and in frequency domain. Results: Expiratory positive airway pressure application affected low frequency (spontaneous breathing: 62.5±4.1 vs slow deep breathing: 28.2±4.2, p<0.001) and high frequency (spontaneous breathing: 37.4±17.3 vs slow deep breathing: 58.9±18.1, p<0.001). Interactions were observed between expiratory positive airway pressure effect and slow deep breathing effect for low frequency (p<0.001), high frequency (p<0.001) and low frequency/high frequency ratio (p<0.001). When patients were stratified by disease’s severity, we identified a significant low frequency reduction (p<0.001) and high frequency increase (p<0.001) for all stages when slow deep breathing was associated with expiratory positive airway pressure. Conclusion: A 5 cmH2O expiratory positive airway pressure during spontaneous and slow deep breathing can elicit an acute response, resulting in a cardiac autonomic control improvement in moderate-to-very severe patients.