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Background: With the expansion of the COVID-19, the study of different oxygen therapy methods has yielded different results. In the current study, we compare the effects of non-invasive ventilation and oxygen therapy through the high-flow nasal cannula. Methods: Non-intensive care unit-admitted COVID-19 patients were randomly divided into two groups. The first group received oxygen therapy with High Flow Nasal Cannula (HFNC) and the second group received Non-Invasive Ventilation (NIV). Clinical conditions and results obtained from laboratory tests were compared in two groups before oxygen therapy, and after 24 and 48 hr. Results: The average age of the participants was 56.25. According to the results, after 24 hr of respiratory intervention, dyspnea was the most frequent in the NIV group with 83.33% and in the HFNC group with 90%. After 48 hr, in the NIV group, nasal flaring was observed with a frequency of 60%, and in the HFNC group, weakness and lethargy were the most common symptoms (56.66%). Comparison of clinical status and laboratory indices of the two groups of patients showed that most of the indices in patients in three time periods were not significantly different, while the results demonstrated that after 24 hours, the mean PaCo2 in the HFNC group was significantly lower than the NIV group (0.002) and the mean PH in the HFNC group was significantly higher than the other group (p=0.039). Conclusion: The effectiveness of using HFNC compared to NIV is the same and shows no significant difference. [ABSTRACT FROM AUTHOR]