This work experimentally investigated the energy performance of several non-fluorinated refrigerant mixtures and their pure components on a prototype of a low-refrigerant charge single-stage water-to-water heat pump. The pure refrigerants tested in the unit were Propane (R-290), Propylene (R-1270) and Dimethyl Ether (DME, R-E170). In addition, the tested mixtures were Propane-CO2, Propylene-CO2, DME-CO2, Propylene-DME at different compositions and temperatures. Total refrigerant charge amounts, including auxiliary pipes and valves, ranged between 190 g and 290 g. Heating capacities ranged between 3.7 kW and 12.2 kW. The highest capacities were obtained by Propylene-CO2 [0.93–0.07]. At high source and sink glide conditions, mixing low amounts of CO2 showed performance enhancements, especially on Propylene and DME. Compared to Propane, DME mixed with 5 % CO2, resulted in up to 12 % COP enhancement, 16 % lower capacity, and 50 % higher limit heating capacity (LHC). Propylene and the low-glide mixture Propylene-DME performed well at low source and sink glides compared to Propane. Measurements on the refrigerant cycle also suggest that the circulating composition of the mixture slightly shifted toward the most volatile component. The results suggest that well-designed refrigerant mixtures containing Propylene, DME and CO2 may enhance efficiency, heating capacity, and the heating capacity at maximum charge while maintaining conventional operating pressures and discharge temperatures.