The emergence of the coronavirus disease 2019 (COVID-19) pandemic has led to a cost and time crisis for most construction projects around the world. Adherence to COVID-19 response guidelines for construction sites may prevent the occurrence of COVID-19 cases, which eliminates the risk of site closure. However, adding a disinfection process to the construction process, as mandated in COVID-19 response guidelines, increases overall construction cost and time. Conversely, however, not adding a disinfection process may result in COVID-19 cases among construction workers, which would delay construction and perhaps even cause closure of the construction site. Therefore, this study analyzed the feasibility of COVID-19 response guidelines for construction sites, especially the addition of a disinfection process, in terms of cost and time. To this end, CYClic Operations NEtwork (CYCLONE) models were developed to simulate the construction process, and a case study was conducted to validate the applicability of the suggested approach. The results showed that compliance with COVID-19 response guidelines increased the number of working days and the construction costs of the subject construction project, but because there was no more risk of construction site closure, the construction delays were short, and the liquidated damages were minimized. Through the method proposed in this study, it is possible to estimate construction cost and time before and after the COVID-19 pandemic; this method could be used to provide data for both owners and contractors to pro-actively recognize and respond to situations or damage caused by the COVID-19 pandemic. The data could also be used as evidence in case of future damages or disputes.