Inadequate refrigerant charges can affect the vapor compression refrigeration systems’ thermal and energy performance. To delve deeper into the subject, this study experimentally evaluated the performance of a domestic refrigerator operating at different refrigerant charges. Some of them simulate refrigerant leaks (70 and 80 g), and some others simulate an excess (100 and 110 g). Through a statistical analysis (Tukey test and control graphs), the temperature data with the greatest impact were analyzed, including the temperatures in the suction and in the compressor casing, the temperatures in the middle position and outlet of the condenser and evaporator, as well as the temperatures in the freezer. The operation of the refrigerator was affected to a greater extent when it worked with an overcharge of 110 g; here, the discharge pressure and the run time increased by 1.3 bar and 21%, respectively, compared to the conditions of the refrigerator operating with the reference charge (86 g). In addition, the excess charge also caused an increase in energy consumption of 0.56 kWh/day and a decrease in EER of 0.5 regarding the reference charge. Finally, the increase in energy consumption was projected to $0.03 USD per day with respect to the reference cost.