There has been increasing interest in clean energy over past few years. Ocean Thermal Energy Conversion (OTEC) power plants have been examined as a viable option for supplying clean energy. This paper evaluated the thermodynamic performance of the OTEC power system. Computer simulation programs were developed under the same conditions but with various working fluids for a closed system, a regeneration system, an open system, a Kalina system, and a hybrid system. The results showed that the regeneration system using R125 showed a 0.17 to 1.56% increase in system efficiency. Moreover, the system can generate electricity when the difference in temperature between the warm and cold seawater inlet temperatures is greater than 15 °C. In addition, the system efficiency of OTEC power plants using the condenser effluent from a nuclear power plant instead of surface water was increased by approximately 2%.