Background and objective Hypercapnia is associated with worse clinical outcomes in exacerbations of COPD. The present study aimed to determine the effects of nasal high flow (NHF) therapy on transcutaneous partial pressure of carbon dioxide (PtCO2) in stable COPD patients. Methods In a single-blind randomized controlled cross-over trial, 48 participants with COPD were allocated in random order to all of four 20 min interventions: NHF at 15 L/min, 30 L/min and 45 L/min or breathing room air with each intervention followed by a washout period of 15 min. The primary outcome measure was PtCO2 at 20 min, adjusted for baseline PtCO2. Secondary outcomes included respiratory rate at 20 min, adjusted for baseline. Results The mean (95% CI) change in PtCO2 at 20 min was −0.6 mm Hg (−1.1 to 0.0), P = 0.06; −1.3 mm Hg (−1.9 to 0.8), P