In high-power systems of proton exchange membrane fuel cells (PEMFC), cooling systems for the balance of plants (BOP) play an extremely important role in maintaining the temperature of the key components of the fuel cell system. To evaluate the effect of the PEMFC BOP cooling system on the fuel cell system efficiency, a Simulink model of the fuel cell system and an AMEsim model of the cooling system for the BOP system are established based on experimental data. A co-simulation is conducted based on the established models to determine the effects of fuel cell stack output power, coolant flowrate, radiator fan speed, and temperature control strategies on the parasitic power consumption and fuel cell system efficiency. The simulation results show that with an increase in the stack output power, coolant flowrate, and radiator fan speed, the parasitic power of the BOP cooling system increases and the system efficiency of PEMFC decreases. With an increase in the opening temperature of the radiator fan, the parasitic power of the BOP cooling system decreases and the system efficiency of the PEMFC increases. Compared with the rule-based control strategy, the radiator fan speed control strategy based on the PID controller achieves lower parasitic power. The research presented in this paper is helpful for further development of efficient fuel cell vehicle thermal management system.