As of March 24, 2020, the Food and Drug Administration (FDA) authorized to bleed the newly recovered from Coronavirus Disease 2019 (COVID-19), i.e., the ones whose lives were at risk, separate Plasma from their blood and inject it to COVID-19 patients. In many cases, as observed the plasma antibodies have cured the disease. Therefore, a four-echelon supply chain has been designed in this study to locate the blood collection centers, to find out how the collection centers are allocated to the temporary or permanent plasma-processing facilities, how the temporary facilities are allocated to the permanent ones, along with determining the allocation of the temporary and permanent facilities to hospitals. A simulation approach has been employed to investigate the structure of COVID-19 outbreak and to simulate the quantity of plasma demand. The proposed bi-objective model has been solved in small and medium scales using
-constraint method, Strength Pareto Evolutionary Algorithm II (SPEA-II), Non-dominated Sorting Genetic Algorithm II (NSGA-II), Multi-Objective Grey Wolf Optimizer (MOGWO) and Multi Objective Invasive Weed Optimization algorithm (MOIWO) approaches. One of the novelties of this research is to study the system dynamic structure of COVID-19’s prevalence so that to estimate the required plasma level by simulation. Besides, this paper has focused on blood substitutability which is becoming increasingly important for timely access to blood. Due to shorter computational time and higher solution quality, MOIWO is selected to solve the proposed model for a large-scale case study in Iran. The achieved results indicated that as the plasma demand increases, the amount of total system costs and flow time rise, too. The proposed simulation model has also been able to calculate the required plasma demand with 95% confidence interval.