In this study we used Nek5000, an open-source, high-order spectral element CFD code developed at Argonne National Laboratory (ANL), to model the coolant flow in spacer grids. Two fuel assembly configurations were studied: 2x2 and 5x5 fuel rod arrangements. The simulations for the 2x2 case were based on previous studies, simulating one span of the 2x2 fuel rod configuration including a surrogate spacer grid and mixing vane design with typical features of spacers for energy production. Dual periodic boundary conditions were applied in the spanwise direction to take the crossflow into consideration. The study of the 5x5 fuel assembly was performed as part of the ANL—Framatome collaboration for advancing computational fluid dynamics (CFD) tools. An advanced numerical model was developed to simulate the experimental setup provided by Framatome. For the 5x5 fuel assembly study, two cases of flow geometry were simulated with Nek5000: balanced and unbalanced configurations. In the balanced flow the coolant was entering the fuel rod assembly through 121 uniformly spaced inlet holes arranged in an 11x11 matrix. The unbalanced case, on the other hand, featured 14 larger holes placed on only one side of the horizontal plane. Nek5000 accepts only hexahedral meshes, which bring a great challenge to the meshing process for a spacer grid fuel assembly. A tet-to-hex meshing strategy was applied to handle the complex geometric features. A tetrahedral mesh was created first, and then each tetrahedral element was converted into four hexahedral elements. Boundary layers were extruded to fit to the exact geometry. In order to account for transient flow characteristics, the large eddy simulation approach was applied in this study. The employed subgrid-scale model relies on explicit filtering, which has been proven valid for many engineering-scale simulations. We present here the simulation results obtained for both the 2x2 and 5x5 fuel assemblies.