The purpose of this paper is to compare the thermal efficiency of an ocean thermal energy conversion (OTEC) cycle using R717 and R22 working fluids. An OTEC system typically operates at the temperature difference between the average warm surface seawater of 30 °C and the cold deep seawater of 8 °C. The temperature difference will then power a turbine to produce electricity. R22 and R717 are two potential working fluids to be used in the OTEC cycle to absorb heat due to their saturation temperature. However, R22 is associated with higher global warming potential and the global warming potential (GWP) of 1,760, compared to R717 with zero GWP. The study shows that the thermal efficiency of R22 is 0.211% higher than R717. Moreover, the thermal power required by the water circuit to cool/heat the OTEC circuit for R717 is 13% higher than R22. However, the required working fluid flow rate of the R717 system is 81.5% lower than R22, making the former significantly smaller in size.