Background In precapillary pulmonary hypertension (PH), nasal high flow therapy (NHF) may favorably alter sympathovagal balance (SVB) and sleep-related breathing through washout of anatomical dead space and alleviation of obstructive sleep apnea (OSA) due to generation of positive airway pressure. Objectives To investigate the effects of NHF on SVB, sleep, and OSA in patients with PH, and compare them with those of positive airway pressure therapy (PAP). Methods Twelve patients with PH (Nice class I or IV) and confirmed OSA underwent full polysomnography, and noninvasive monitoring of SVB parameters (spectral analysis of heart rate, diastolic blood pressure variability). Study nights were randomly split into four 2-h segments with no treatment, PAP, NHF 20 L/min, or NHF 50 L/min. In-depth SVB analysis was conducted on 10-min epochs during daytime and stable N2 sleep at nighttime. Results At daytime and compared with no treatment, NHF20 and NHF50 were associated with a flow-dependent increase in peripheral oxygen saturation but a shift in SVB towards increased sympathetic drive. At nighttime, NHF20 was associated with increased parasympathetic drive and improvements in sleep efficiency, but did not alter OSA severity. NHF50 was poorly tolerated. PAP therapy improved OSA but had heterogenous effects on SVB and neutral effects on sleep outcomes. Hemodynamic effects were neutral for all interventions. Conclusions In sleeping PH patients with OSA NHF20 but not NHF50 leads to decreased sympathetic drive likely due to washout of anatomical dead space. NHF was not effective in lowering the apnea-hypopnoea index and NHF50 was poorly tolerated.