The sudden onset of the coronavirus (SARS-CoV-2) pandemic has resulted in tremendous loss of human life and economy in more than 210 countries and territories around the world. While self-protections such as wearing masks, sheltering in place and quarantine policies and strategies are necessary for containing virus transmission, tens of millions of people in the U.S. have lost their jobs due to the shutdown of businesses. Therefore, how to reopen the economy safely while the virus is still circulating in population has become a problem of significant concern and importance to elected leaders and business executives. In this study, mathematical modeling is employed to quantify the profit generation and the infection risk simultaneously from a business entity’s perspective. Specifically, an ordinary differential equation model was developed to characterize disease transmission and infection risk. An algebraic equation is proposed to determine the net profit that a business entity can generate after reopening and take into account the costs associated of several protection/quarantine guidelines. All model parameters were calibrated based on various data and information sources. Sensitivity analyses and case studies were performed to illustrate the use of the model in practice. The results show that with a combination of necessary infection protection measures implemented, a business entity may stand a good opportunity to generate a positive net profit while successfully controlling the within-business infection prevalence under that in the general population. The use of personal protective equipment (PPE) is also found of significant importance, especially at the early stage of business reopening.