The high integration of Renewable Energy Sources (RES) for electricity generation has been widely discussed worldwide in order to ensure long-term sustainable energy supply but also because the electricity sector stands out as a leading climate change driving force. Although several studies have recognized these challenges, research has yet to systematically investigate what would be the effects of different Energy Efficiency Measures (EEMs) on power systems with a high share of RES, especially from hydropower. Therefore, the primary aim of this paper is to quantitatively evaluate the economic impact of different levels of energy efficiency investments in systems with a high share of RES. The Brazilian electricity system is an important example of a power system which deeply relies on RES and therefore it was used in this research to allow a deeper insight into the effects of EEMs and to evaluate the effectiveness of these strategies. Findings of this study suggest that the implementation of EEMs may result in a reduction (comparatively to the BAU scenario) in the new installed system capacity varying between 1.8% and 9.0% and from 1.2% to 3.7% for the total CO2 emissions (for reductions in the final electricity demand from 1% to 5% respectively). This comes with a decrease in the overall system costs varying between 0.3% (Case 1) to 0.9% (Case 5) comparatively to the BAU scenario. The results provide further support for the hypothesis that the economic impacts of EEMs are driven largely by the share of RES and this type of measures may provide holistic benefits for the power system including not only economic advantages but also environmental and social improvements.