Air-breathing polymer electrolyte fuel cells (PEMFCs) are expected to play an important role in the development of sustainable portable and mobile devices, such as unnamed aerial vehicles, motorbikes or laptops. In this work, the performance of air-breathing PEMFCs with a columnar cathode plate design is examined by means of a 3D two-phase, non-isothermal model, and compared against experimental data. The results show that the performance is highly influenced by the cell orientation, namely horizontal (material plane perpendicular to gravity) versus vertical (material plane parallel to gravity). Oxygen transport in horizontal cells is mainly dominated by diffusion, leading to oxygen shortage toward the cell center and an inhomogeneous current density distribution. In contrast, oxygen transport in vertical cells is assisted by natural convection, enhancing oxygen transport throughout the cell and increasing the current density homogeneity. Water saturation is preferentially accumulated close to the cell center, being larger in horizontal cells due to the lower water removal rate of the cathode plate.