Based on the literature review, it is difficult to find an accurate model for the system efficiency of a PEMFC with the consideration of the fuel energy, thermal energy for preheating and humidification, and compression work for BOP components. In this study, athree-dimensional computational fluid dynamics simulation was carried out to overcome the limitations of the previous studies. A unit cell with a serpentine flow field was simulated with consideration of the compression work for the BOP component along with the heat for preheating and humidification. The operating conditions were optimized using the response surface methodology by considering both the fuel cell output and system efficiency. Theperformances of each energy component were also compared based on a case study. In addition, the effects of operating parameters such as the temperature, relative humidity, and stoichiometric ratio on the fuel cell power, system efficiency, and energy component were investigated.