Rationale and Objective: Various forms of Non-invasive respiratory support (NRS) have been used during COVID-19, to treat Hypoxemic Acute Respiratory Failure (HARF), but it has been suggested that the occurrence of strenuous inspiratory efforts may cause Self Induced Lung Injury(P-SILI). The aim of this investigation was to record esophageal pressure, when starting NRS application, so as to better understand the potential risk of the patients in terms of P-SILI and ventilator induced lung injury (VILI)., Methods and Measurements: 21 patients with early de-novo respiratory failure due to COVID-19, underwent three 30 min trials applied in random order: high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and non-invasive ventilation (NIV). After each trial, standard oxygen therapy was reinstituted using a Venturi mask (VM). 15 patients accepted a nasogastric tube placement. Esophageal Pressure (ΔPes) and dynamic transpulmonary driving pressure (ΔPLDyn), together with the breathing pattern using a bioelectrical impedance monitor were recorded. Arterial blood gases were collected in all patients., Main Results: No statistically significant differences in breathing pattern and PaCO 2 were found. PaO 2 /FiO 2 ratio improved significantly during NIV and CPAP vs VM. NIV was the only NRS to reduce significantly ΔPes vs. VM (-10,2 ±5 cmH20 vs -3,9 ±3,4). No differences were found in ΔPLDyn between NRS (10,2±5; 9,9±3,8; 7,6±4,3; 8,8±3,6 during VM, HFNC, CPAP and NIV respectively). Minute ventilation (Ve) was directly dependent on the patient's inspiratory effort, irrespective of the NRS applied. 14% of patients were intubated, none of them showing a reduction in ΔPes during NRS., Conclusions: In the early phase of HARF due to COVID-19, the inspiratory effort may not be markedly elevated and the application of NIV and CPAP ameliorates oxygenation vs VM. NIV was superior in reducing ΔPes, maintaining ΔPLDyn within a range of potential safety., (Copyright © 2022. Published by Elsevier B.V.)