We are developing an Emergency Respiratory Support Lung (ERSL) to provide pulmonary assist for acute lung failure. A rotating hollow fiber membrane bundle actively mixes blood for efficient gas transfer and provides pumping ability required for its intended paracorporeal veno-venous operation. A CFD model was developed to support the design, and experimental testing of prototypes. Applicable equations were solved in 2D and 3D domains using FLUENT. Two different approaches were used; one utilized a porous media model and another was based on evaluation of flow around individual fibers. Both simulations showed that the rotating fiber bundle accelerates fluid entering the bundle, and the width of the acceleration zone does not exceed two fiber diameters. Simulation at 1500 rpm predicted that relative velocity inside the fiber bundle was five times greater than in stationary bundle and the ERSL was able to generate a pressure head increase across the device. CFD analysis showed that the area of maximum shear rate (200 s−1) for the stationary bundle case was in the outlet port vicinity; whereas the rotational case at 1500 rpm predicted a maximum shear rate of 3000 s−1at the housing's stationary walls. CFD predictions were compared to pressure measurements and dye injection flow visualization in order to validate the models. We obtained qualitative agreement between simulations and experiments. Optimization of inlet port geometry was performed to avoid stagnant zones and decrease probability of clotting. Evaluation of hemolysis using a CDF model will be performed for experimental ERSL prototype.