<p>This study investigates the influence of flow field design and gas diffusion layer (GDL) and catalyst layer (CL) tortuosity on liquid water saturation in proton exchange membrane fuel cells (PEMFCs) using a three-dimensional, non-isothermal, multiphase computational fluid dynamics (CFD) model. Three flow field configurations—serpentine, parallel, and interdigitated—are analyzed while varying GDL and CL tortuosity (<i>τ</i> = 1.5, 2.0, 2.5) to examine their combined impact on liquid water distribution, effective diffusion coefficients, and cell performance. The model incorporates an effective diffusion framework accounting for tortuosity due to GDL and CL microstructure and liquid water saturation. Results show that higher tortuosity reduces effective diffusion coefficients and increases mass transport limitations, particularly under high-load conditions. The serpentine flow field with low tortuosity (<i>τ</i> = 1.5) achieves the lowest liquid water saturation and highest current densities, demonstrating superior water removal. The interdigitated flow field outperforms the parallel configuration by approximately 19% due to forced convection, enhancing reactant transport. The parallel flow field shows the lowest performance, being more prone to water flooding. These findings highlight the importance of flow field design and GDL/CL tortuosity in optimizing PEMFC performance, offering insights for developing more efficient fuel cells. The interaction between channel types and GDL tortuosity is explicitly analyzed, clarifying their combined effects on PEMFC performance.</p> Graphical Abstract <p></p>