Abstract Currently, most bioseparation processes used for purification of bio-pharmaceutical products such as vaccines, monoclonal antibodies, and enzymes use resin-based column chromatography. Resolution and productivity are two of the major factors that should be optimized in any purification process. While column chromatography techniques give high-resolution and consequently very high product quality, they are slow, leading to low-productivity and high production cost. One of the alternatives to resin-based columns is membrane chromatography, where a stack of membrane sheets is used as chromatographic media. Membrane chromatography is a fast and scalable technique; however, it is not commonly used for some of the critical purification steps due to its low-resolution capability. A technique newly developed in our group called laterally-fed membrane chromatography (or LFMC) combines high-resolution separation with high-productivity. It is, therefore, suitable for rapid, multicomponent protein purification. LFMC not only gives higher resolution than other membrane chromatography devices, it gives comparable resolution to that obtained with equivalent resin-based packed bed columns, even at significantly higher flow rates, as demonstrated in our previous work. This paper examines the system fluid dynamics in an LFMC device using computational fluid dynamics (CFD) simulations and explains the reasons behind its superior separation attributes.