Objective Given the high mortality and prolonged duration of mechanical ventilation of COVID-19 patients, we evaluated the safety and efficacy of hyperbaric oxygen for COVID-19 patients with respiratory distress . Methods This is a single-center clinical trial of COVID-19 patients at NYU Winthrop Hospital from March 31 to April 28 , 2020 . Patients in this trial received hyperbaric oxygen therapy at 2.0 atmospheres of pressure in monoplace hyperbaric chambers for 90 minutes daily for a maximum of five total treatments . Controls were identified using propensity score matching among COVID-19 patients admitted during the same time period . Using competing-risks survival regression, we analyzed our primary outcome of inpatient mortality and secondary outcome of mechanical ventilation . Results We treated 20 COVID-19 patients with hyperbaric oxygen . Ages ranged from 30 to 79 years with an oxygen requirement ranging from 2 to 15 liters on hospital days 0 to 14 . Of these 20 patients, two (10 %) were intubated and died, and none remain hospitalized . Among 60 propensity-matched controls based on age, sex, body mass index, coronary artery disease, troponin, D-dimer, hospital day, and oxygen requirement , 18 (30 %) were intubated , 13 (22 %) have died, and three (5 %) remain hospitalized (with one still requiring mechanical ventilation). Assuming no further deaths among controls, we estimate that the adjusted subdistribution hazard ratios were 0.37 for inpatient mortality (p=0.14) and 0.26 for mechanical ventilation (p=0.046). Conclusion Though limited by its study design, our results demonstrate the safety of hyperbaric oxygen among COVID-19 patients and strongly suggests the need for a well-designed, multicenter randomized control trial.