Background. The paper discusses the use of a thermal helium-oxygen mixture (t-He/O2 ), a novel technology, in treating patients with the 2019-nCoV acute respiratory disease (COVID-19) who develop life-threatening respiratory failure. Aim-to evaluate the safety and efficacy of t-He/O2 inhalation combined with standard therapy in the treatment of acute respiratory failure in patients with COVID-19. Materials and Methods. This was a single-center, randomized, prospective study of 70 patients with COVID-19. All patients were divided into two groups: In Group 1 (n = 38) patients received t-He/Î2 in addition to the standard COVID-19 treatment; and in Group 2 (n = 32) patients were given the standard treatment in accordance with the Clinical Treatment Guidelines for patients with COVID-19, developed by the Ministry of Health of the Russian Federation. The male/female ratio was 18/20 in Group 1 and 18/14 in Group 2. The mean age of the patients in the study was 53.5 years (43; 62): 56 years (42; 64) in Group 1 and 52 years (43; 66) in Group 2. All patients had computed tomography (CT) signs of lung injury: Ground-glass opacities and areas of consolidation. SARS-CoV-2 RNA was detected in 30 Group 1 patients and 28 Group 2 patients. The patients were matched by sex, age, body mass index (BMI), area of pulmonary involvement, and laboratory findings. All patients provided voluntary informed consent to participate in the study and signed a consent form. Results. Inhalation of thermal helium-oxygen mixture combined with standard therapy did not cause any procedure-related side effects in any of the patients. The following changes were observed in all patients: PO2/FiO2 , SpO2 , and lymphocyte counts increased, C-reactive protein (CRP) levels decreased, and D-dimer and ferritin levels returned to normal. In Group 1 statistically significant changes in the above-mentioned parameters were seen within three days, while in Group 2 the same changes were observed between Days 7 and 10 of treatment. In Group 1 patients cleared SARS-CoV-2 within 48-72 hours after initiation of inhalation, which was confirmed by polymerase chain reaction (PCR), and in Group 2 virus elimination was achieved within 72-168 hours. Conclusion. The addition of inhalation of a thermal gas mixture of helium and oxygen (t-He/O2) to the standard therapy for patients with SARS-CoV-2 infection, CT signs of pneumonia (grades CT2 or CT3), and acute respiratory failure improves gas exchange, contributes to a more rapid virus elimination, and indirectly reduces inflammation.