Due to the increase in the amount of copper sulphide minerals processed through concentration processes and the need to improve the efficiency of these production processes, the development of theoretical models is making an important contribution to generating a better understanding of their dynamics, making it possible to identify the optimal conditions for the recovery of minerals, the impact of the independent variables in the responses, and the sensitivity of the recovery to variations in both the input variables and the operational parameters. This paper proposes a method for modeling, sensitizing, and optimizing the mineral recovery in rougher cells using a discrete event simulation (DES) framework and the fitting of analytical models on the basis of operational data from a concentration pilot plant. A sensitivity analysis was performed for low, medium, and high levels of the operative variables and/or parameters. The outcomes of the modeling indicate that the optimum mineral recovery is reached at medium levels of the flow rate of gas, bubble size, turbulence dissipation rate, surface tension, Reynolds number of bubble, bubble–particle contact angle, superficial gas velocity and gas hold-up in the froth zone. Additionally, the optimal response is reached at maximum levels of particle size and density and at minimum levels of bubble speed, fluid kinematic viscosity and fluid density in the sampled range. Finally, the recovery has an asymptotic behavior over time; however, the optimum recovery depends on an economic analysis, examining the marginalization of the response over time in an operational context.