In this study, the system efficiency of the PEMFC was evaluated at elevated temperature and relative humidity conditions. Three-dimensional steady-state simulations were conducted in a unit cell of a PEMFC with a serpentine flow field. The system efficiency wasestimated by considering the fuel energy, the heat required for preheating/humidification and compression work. Operating parameters such as the temperature, relative humidity and stoichiometric ratio were optimized using the response surface methodology by considering both the power output and system efficiency. The system efficiency decreased with increasing current density because both the fuel energy and the thermal energy for preheating andhumidification linearly increased even though the increasing slope of the power density gradually decreased. The optimal operating parameters were 90.6℃, 100.0%, and 2.07 for the temperature, relative humidity, and stoichiometric ratio, respectively. In addition,the power output and system efficiency were 1.28 W and 15.8% at the optimal condition, respectively. The optimal condition led to a relatively high system efficiency with allowable cell voltage and power output. In addition, the power output increased with the increase in the operating temperature, but the system efficiency dramatically decreased because of the exponentially increased saturation vapor pressure and thermal energy for preheating/humidification. However, since the ionic conductivity of the membrane was strongly influenced by the relative humidity, the system efficiency can be more effectively improved by increasing relative humidity rather than increasing operating temperature.