Closed cycle ocean thermal energy conversion (CC-OTEC) is a way to generate electricity by the sea water temperature difference from the upper surface to the different depth. This paper presents the performance of a 15 kW micropower CC-OTEC system under different working fluids. The results show that both butane and isobutane are not proper working fluids for the CC-OTEC system because the inlet stable operating turbine pressure is in a very narrow range. R125, R143a, and R32, especially R125, are suggested to be the transitional working fluids for CC-OTEC system for their better comprehensive system performance. Moreover, it is recommended that propane should be a candidate for the working fluid because of its excellent comprehensive properties and environmental friendliness. However, propane has inflammable and explosive characteristics. As for the natural working fluid ammonia, almost all performance properties are not satisfactory except the higher net output per unit sea water mass flow rate. But ammonia has relative broader range of the stable operating turbine inlet pressure, which has benefits for the practical plant operation.