Macroscopic computational fluid dynamic (CFD) simulations are widely used to investigate blood flow in the hollow fiber membrane (HFM) bundle of oxygenator devices. Darcys porous media models with isotopic permeabilities are used to implement hydrodynamic flow resistance of the HFMs. An experimental approach was developed to determine three-dimensional permeabilities of HFM bundles of different fiber configurations. For easier determination of three-dimensional permeabilities of other fiber configurations in the future, a second approach was developed based on microscopic CFD. It is assumed that anisotropy matters in a device with a multi-dimensional flow field. For that reason, particle image velocimetry (PIV) was used for the first time in an oxygenator, to identify a device with that kind of expected flow field. Finally, to evaluate the influence of anisotropic permeabilities on a macroscopic flow field, macroscopic anisotropic CFD simulations were compared to state-of-the-art isotropic simulations in the oxygenator. Experimental as well as microscopic CFD results show that especially the 24° fiber configuration has a clearly anisotropic permeability characteristic. This fiber configuration is very common in wrapped oxygenator devices. The NeonatOx (proprietary of CVE) is a wrapped device and PIV results show that it has a complex and threedimensional flow field. Finally, macroscopic CFD results confirm that the anisotropic characteristic of the HFM bundle influences the flow field in terms of stagnation areas, shunt flows, and directional velocities in the bundle. It is shown in this work that the permeabilities of fiber bundles in oxygenators are anisotropic and that this property influences the numerically simulated macroscopic flow field.