BACKGROUND: Although positive airway pressure (PAP) therapy is effective for treating obstructive sleep apnea (OSA), some patients with severe OSA are intolerable to this treatment, which may lead to an increase in the mortality and morbidity of cardiovascular diseases. We investigated the relationship between heart rate variability (HRV) and sleep parameters during natural sleep and treatment of patients with OSA. MATERIALS AND METHODS: This was the cross-sectional observation study. Patients were 17 males with severe OSA who were unable to accept continuous PAP. Standard polysomnography was performed for two consecutive nights, i.e., during natural sleep and following night with bilevel PAP (BiPAP) treatment. Time-dependent responses of the amplitudes of low frequency (LF), very low frequency (VLF), and high frequency components of HRV were assessed with the technique of complex demodulation. RESULTS: Apnea-hypopnea index, oxygen desaturation time, and percentage of stage 1 sleep were significantly reduced, whereas the percentages of rapid eye movement and stages 3 + 4 sleep were increased, by BiPAP treatment. Therapy also reduced the amplitudes of VLF and LF components of HRV. Difference in amplitudes of VLF during natural sleep and treatment with BiPAP was significantly correlated with difference in percentages of stage 1 and stages 3 + 4 sleep. CONCLUSION: Therapy-induced amelioration of OSA and sleep quality was accompanied by decrease in the amplitudes of VLF components of HRV. The VLF component may thus reflect physiological changes in both autonomic activity and sleep structure and serve as an objective marker for therapeutic efficacy in patients with severe OSA.