A framework to generate predictive simulations is proposed to investigate the influence of system's mass on manual wheelchair locomotion. The approach is based on a model of wheelchair propulsion dynamics and an optimal control formulation. In this study, predictive simulations of steady-state wheelchair locomotion are generated for different combinations of model mass and uphill slope inclination angle. The results show that the influence of system's mass is negligible in level surfaces in steady-state, a finding which agrees with experimental observations in the literature. On the other hand, the results show that the influence of mass on slopes is critical, with large increases in propulsion effort with system's mass, even for slight inclination angles. This shows the importance of reducing wheelchair mass for improving locomotion performance, particularly in overcoming obstacles and ramps. Decreasing the wheelchair's mass may not be sufficient. Therefore, and on the light of these findings, we propose the reduction of system's apparent mass through the implementation of an impedance control scheme in powerassisted wheelchairs.