Limestone in volcanic basements has been identified as a hazard in terms of edifice stability due to the propensity of calcite to decompose into lime and CO2 at high temperatures (>600 °C), causing a decrease in mechanical strength. To date, such hypotheses have been tested by experiments performed at ambient pressure. The present work determines the mechanical strength of limestone under sub-volcanic conditions of pressure and temperature and evaluates the effect of calcite decomposition. To this end, we use Mt. Etna as a case study, deforming sub-Etnean carbonate samples under triaxial compression using a Paterson deformation apparatus. We evaluate the effect of thermal decomposition of calcite on sample strength by comparing closed and open systems and measuring the permeability evolution under static conditions. Mechanical and micro-structural observations at a constant strain rate of 10−5 s−1 and at a confining pressure of 50 MPa indicate that the rocks are brittle up to and including 300 °C. At higher temperatures the deformation becomes macroscopically ductile, i.e., deformation is distributed throughout the sample. The brittle to ductile transition is accompanied by an irreversible permeability decrease from ∼10−17 to ∼10−19 m2 between 200 and 600 °C. We present new evidence that permanent change in permeability is due to ductile processes closing the initial pore space. Samples deformed at temperatures up to 900 °C do not contain any decarbonation products. At these temperatures, permeability is sufficiently low to permit CO2 pore pressures to increase, thereby increasing local CO2 fugacity, which in turn strongly limits the decarbonation reaction. We note that, for non-pure calcite rocks, permeability might be sufficient to allow decarbonation reactions to occur. As such, variability in lithologies may slightly influence the efficiency of decarbonation reactions. We conclude that, in a closed system, the instability of Mt. Etna is related to high temperature induced ductile flow of basement limestone rather than chemical/mineralogical changes. This may have important implication for the stability of volcanoes within carbonate-rich basement, as carbonates become significantly weak at high temperatures, which may increase the risk of sector collapse.