Background and objectives: Patients with interstitial lung disease (ILD) experience early symptoms of dyspnoea and leg fatigue during exercise together with severe and rapid oxygen desaturation. Heated and humidified nasal high flow oxygen (NHF) has been proven to enhance exercise endurance and physiological parameters in COPD patients. This study aims to evaluate the effect of NHF on exercise tolerance in ILD patients.Methods: Twenty-five patients (10 female) with severe ILD performed three constant-load (70% maximal workload) cycling tests to exhaustion under different breathing conditions: room air, oxygen supplementation (4 L min-1 O2) and NHF (inspiratory O2 fraction 0.5, 30-50 L min-1, heated 34 °C and humidified).Results: Endurance time was significantly longer with NHF (618 ± 297 s) compared to O2 (369 ± 217 s, p < 0.001) and room air (171 ± 76 s, p < 0.001). Kinetics of oxygen desaturation, chronotropic response, dyspnoea and leg fatigue sensations were delayed with NHF. At exhaustion with NHF, compared to the two other conditions, oxygen desaturation was less severe while heart rate, dyspnoea and leg fatigue were similar.Conclusion: NHF significantly improved endurance time, physiological parameters and sensations during exercise in severe ILD patients. NHF may be useful to improve functional capacities and facilitate pulmonary rehabilitation in ILD.