This paper presents an experimental investigation of the effect of R290/R600a refrigerant mixtures on the performance of variable speed hermetic compressors used in household refrigeration. In this context, a small-capacity compressor test stand is introduced and four different compositions of R290/R600a mixtures are studied in detail. R290 composition in the refrigerant mixture varies between 40–70% by mass weight. Performance outcomes of the mixtures are compared to baseline refrigerant R600a. The influence of R290 composition in refrigerant mixture over COP, refrigerant mass flow rate and power consumption rates are explored in the present study. Moreover, the effect of compressor speed, evaporation and condensation temperature on the compressor performance are studied via steady-state experimental tests. It has been concluded that increasing the mass weight of R290 in the mixture yields higher power consumption rates, yet it has brought a significant increase in the refrigerant mass flow rate, thus enabling a higher COP. The optimum compressor speed is found to be approximately 2100 rpm for the tested hermetic reciprocating compressor. The COP increases with the increments of evaporation temperature and decrements of the condensation temperature. The COP of the refrigeration cycle is 10–20% greater than that of R600a depending on the composition of the refrigerant mixtures and operating conditions.