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Computational Fluid Dynamics (CFD) has been increasingly adopted as a design tool for the simulation of UV disinfection efficiency and the optimization of the configuration of a UV reactor. However, the performance of CFD with different turbulence closures may vary significantly. In the present study, an experimental evaluation was performed to assess the performance of CFD with five Reynolds Averaged Navier–Stokes (RANS) turbulence closures and three Large Eddy Simulation (LES) sub-grid scale (SGS) models. A simplified crossflow reactor with a single lamp sleeve was fabricated for the experimental measurements and numerical simulations. Overall, the superior performance of LES compared to RANS models in flow predictions within a complex configuration is demonstrated.