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This article is focused on investigating the mathematical model calibration of a reaction–diffusion system arising in the mathematical model of the spread of an epidemic in a society. We consider that the total population is divided into two classes of individuals, called susceptible and infectious, where a susceptible individual can become infectious, and that upon recovery, an infected individual can become susceptible again. We consider that the population lives in a spatially heterogeneous environment, and that the spread of the dynamics is governed by a reaction–diffusion system consisting of two equations, where the variables of the model are the densities of susceptible and infected individuals. In the reaction term, the coefficients are the rates of disease transmission and the rate of infective recovery. The main contribution of this study is the identification of the reaction coefficients by assuming that the infective and susceptible densities at the end time of the process and on overall spatial domain are observed. We apply the optimal control methodology to prove the main findings: the existence of positive solutions for the state system, the existence of at least one solution for the identification problem, the introduction of first-order necessary conditions, and the local uniqueness of optimal solutions. [ABSTRACT FROM AUTHOR]