This work introduces a pumpless high-pressure Soxhlet cross-current solid-liquid extraction method using liquid CO2 and hydrated ethanol for studying the decaffeination of yerba mate. By combining experimental results with thermodynamic modelling, a comprehensive evaluation of the impact of the co-solvent composition is achieved. It is observed that an ethanol/water mixture with a specific composition of 85 wt% is optimal under mild operating conditions (283 K and 4.5 MPa) for extracting caffeine from chopped yerba mate leaves with a negligible co-extraction of caffeoyl derivative antioxidants. The obtained selectivity, together with the phase equilibrium simulation, provide evidence of the significant potential of liquid CO2 extraction as a decaffeination alternative for yerba mate. Thus, high-pressure Soxhlet extraction serves as simple technique to access valuable experimental information with potential for the conceptual design of further scalable semi-continuous processes.