Objectives: This study aims to compare the resources invested during the SARS and COVID-19 epidemics, analyze and compare resources invested by a medical center and a regional hospital during SARS, and estimate the possible investment of resources (including expenses and costs) by the hospitals in different stages of epidemic development. Methods: Compare the different epidemics and hospitals at different levels based on retrospective data, and estimate the investment of resources. Results: A medical center invested 70.34 million worth of resources during SARS, mainly for setting up negative-pressure isolation rooms and a fever clinic (accounting for about 50% of the total investment), whereas the investment during COVID-19 is mainly on anti-epidemic supplies and special allowances for healthcare workers. There is a high level of correlation between investment in anti-epidemic resources by a medical center/regional hospital and the scale of a hospital. Moreover, a medical center estimates that when COVID-19 develops to the most severe stage, the investment will be around 43.04 million (excluding cost allocation), that is about 61% of the expenditure during SARS, and around 53.34 million (including cost allocation), about 76% of the SARS expenditure, at Purple Level 2 status. At the time of SARS, with no similar experience before, hospitals were caught unprepared upon the sudden outbreak, with no negative-pressure isolation facilities. Immense investment had to be made in this resource to accommodate confirmed cases. Although the COVID-19 epidemic is severe, with the negative-pressure isolation facilities already established and the advance deployment already adopted by both the government and the medical center, the epidemic has been kept in control to date. Conclusions: Due to the unpredictability of the epidemic, the time when the epidemic will end is unpredictable, and this will constrain the hospitals' ability to estimate the investment in anti-epidemic resources. The length of a certain stage of epidemic, the severity of the epidemic, the government's anti-epidemic policy, and the result of the hospitals' implementation of anti-epidemic measures all affect the amount of investment in resources. When combating the epidemic, hospitals will have reduced income, and hospitals may face cash flow problem if no government funding is provided. To give back up for the hospitals' anti-epidemic efforts, the government should provide timely financial support for the hospitals to help them overcome the challenge.