The perfusion of blood affects the estimation of diffusivities, especially fast components such as free water. Here, we acquired human data to demonstrate the applicability of a three-compartment model for the joint estimation of tissue diffusivities, free water, and the perfusion fraction. We evaluated the feasibility of the model by comparing a multiple b-value approach with a shorter, clinically feasible approach. The conclusion is that the two-compartment free-water estimation is affected by both water and blood. The three-compartment model disentangles these effects, useful in distinguishing between changes originating from capillary blood from those originating from the extracellular space.