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This study investigates the impact of melting/binding rates (referred to hereafter as the parameters) over the polymers and monomers on the dynamics of carbon-monoxide-mediated sickle cell hemoglobin (HbS) de-polymerization. Two approaches, namely the traditional sensitivity analysis (TSA) and the multi-parameter sensitivity analysis (MPSA), have been developed and applied to the mathematical model system to quantify the sensitivities of polymers and monomers to the parameters. The Runge-Kutta method and the Monte-Carlo simulation are employed for the implementation of the sensitivity analyses. The TSA utilizes the traditional sensitivity functions (TSFs). The MPSA enumerates the overall effect of the model input parameters on the output by perturbing the model input parameters simultaneously within large ranges. All four concentrations (namely, de-oxy HbS monomers, CO-bound HbS monomers, de-oxy Hbs polymer and CO-bound HbS polymer) as model outputs, and all four binding/melting rates (namely, the CO binding and melting rates for polymers and monomers) as input parameters are considered in this study. The sensitivity results suggest that TSA and MPSA are essentially consistent.