Twenty-two patients hospitalized with severe COVID-19 were randomized to receive oxygen therapy using a high-flow nasal cannula oxygen system (n=22) or conventional oxygen therapy (n=10). Outcomes of interest included vitals (i.e., heart rate; respiratory rate; PaO2/FiO2 oxygenation index), infection indexes (C-reactive protein [CRP]; procalcitonin [PCT]; white blood cell count; lymphocyte count), and length of stay in the hospital and intensive care unit (ICU). Vitals and infection indexes were assessed up to 72 hours post-treatment. Results revealed significantly favourable oxygenation indices up to 72 hours, lower heart rate and respiratory rate at 6 hours, favourable lymphocyte count and CRP levels after application, and short length of ICU stay in the high-flow oxygen therapy group compared to the conventional group (p<0.05 for all).