A numerical scheme for the effect of flow-field orientation on water management in PEM fuel cell is developed. Since there are limitations on the location of proton exchange membrane fuel cell such as portable applications, different configurations are used for proper water management. Therefore, the best configuration must be chosen for the most efficient and stable operation of the fuel cells. In this research, a 3D numerical model is proposed based on the VOF method in order to simulate the effects of gravity on the gas liquid two-phase flow in a full-scale single-serpentine flow-field. This model, which is validated by the experimental results, considers the microstructure of the gas diffusion layer by two square pores in every cross section along the channels. The simulations are done for the vertical and horizontal fuel cells. The effects of water coverage ratios and flow regimes on pressure drop and the resulting parasitic power loss are investigated for different configurations. In the vertical orientation, the channels are placed horizontally or vertically in each configuration. The results reveal that in the vertical cells, when the channels are located horizontally and the inlet manifold is embedded on the upper side of the flow-field, the pressure drop is the lowest. The reason is that the film flow is formed in the channels and the gravity assists in the water removal. However, when both the cell and channels are vertical and the cathode inlet manifold is placed on the bottom of the flow-field, the pressure drop and the resulting parasitic power is the highest. This is due to the gravity is against the water purging from the elbows leading to formation of long plugs along the channels. The present numerical model can be used for simulation of two-phase flow in channels of the serpentine flow-field at any cell orientation angle by changing the gravity direction in the model.