From 2019 to now, the world economy, including Vietnam, has been seriously affected by the Covid-19 pandemic. The paper's main idea showed that the complicated and prolonged Covid-19 epidemic is causing many adverse effects on all economic and social aspects, including the banking industry. The implementation of social distancing to prevent and control the Covid-19 epidemic has partly influenced enterprises' production and business processes and reduced commercial banks' profitability. However, thanks to the promotion of digitization, the operation of credit institutions currently maintains stability, ensuring smooth and safe transactions and bringing profits. Data collection methods: the author collected data from 25 commercial banks listed on the stock exchange from 2009 to 2020 and 300 observations (balanced panel data) extracted from websites and the General Statistics Office of Vietnam. The subject and the goal of the research analyzed vital factors affecting the profitability of commercial banks and the impact Covid-19 epidemic on the profitability of commercial banks listed on the Vietnam stock market. Besides, the author used the method applied to the models analyzed quantitatively through regression to select the appropriate model, the generalized method of moments (SGMM) system. The research findings showed the business profitability of commercial banks in the context of the Covid-19 epidemic, and eight hypotheses were accepted with a 5% significance level. Finally, the research results gave management implications to enhance the profitability of commercial banks in Vietnam. Besides, the study value helps the Government and State Bank are not immune to adverse impacts, and several recommendations have been proposed to overcome these harmful effects.