The present study investigates the effects of non-uniformity in a bundle’s porosity by considering a model channel made up of “dense” (low porosity) and “loose” (high porosity) regions. In a first, simplified, approach these regions are treated as non-interacting porous media and previously obtained computational results are used for the Darcy permeability and the Sherwood number. In a second, and more complete, approach 3-D CFD simulations are conducted for a checkerboard arrangement of alternately “dense” and “loose” regions with square-arrayed fibers, accounting for entry effects and for interactions between regions. Non-uniformity causes a significant increase of the permeability and a strong reduction of the Sherwood number. These effects are larger, approaching those obtained for non-interacting regions, if the regions’ length scale is large. The attainment of fully developed conditions is greatly shifted forward in non-uniform bundles and the mass transfer development length may largely exceed the physical length of most hollow-fiber devices.