Refrigerants of the conventional cooling systems contribute to global warming and ozone depletion significantly, therefore it is necessary to develop new cooling systems that use renewable energy resources and waste heat to perform the cooling function with eco-friendly working fluids. To address this, the present study introduces and analyzes a novel regenerative thermo-mechanical refrigeration system that can be powered by renewable heat sources (solar, geothermal, or waste heat). The system consists of a novel expander–compressor unit (ECU) integrated with a vapor-compression refrigeration system. The integrated system operates at the higher-performance supercritical conditions of the working fluids as opposed to the lower-performance subcritical conditions. The performance of the system is evaluated based on several indicators including the power loop efficiency, the coefficient of performance (COP) of the cooling loop, and the expander–compressor diameters. Several working fluids were selected and compared for their suitability based on their performance and environmental effects. It was found that for heat source temperature below 100 °C, adding the regenerator to the system has no benefit. However, the regenerator increases the power efficiency by about 1% for a heat source temperature above 130 °C. This was achieved with a very small size regenerator (Dr = 6.5 mm, Lr = 142 mm). Results show that there is a tradeoff between high-performance fluids and their environmental effects. Using R32 as a working fluid at heat source temperature Th = 150 °C and cold temperature Tc1 = 40 °C, the system produces a cooling capacity of 1 kW with power efficiency of 10.23%, expander diameter of 53.12 mm, and compressor diameter of 75.4 mm.