A procedure based on experimental tests and Discrete Element Method (DEM) [1] was developed in this study to investigate the mechanical effects of the interaction between CO2 and carbonate rocks. Two subsurface procedures motivate this study: enhanced oil recovery and CO2 sequestration. The former is a more established procedure that the oil and gas industry performs to increase the amount of oil produced from the reservoir by injecting CO2 or CO2 with water into the reservoir. The latter consists of injecting CO2 into geological deposits to reduce the greenhouse gases in the atmosphere. The injected CO2, when dissolved in water, forms carbonic acid, which reacts with the host rock, altering some of its geomechanical properties. This study focuses on carbonate rocks, a common pre-salt reservoir rock in Brazilian fields, being considered a candidate for CO2 sequestration. Therefore, experimental tests on Indiana Limestone samples were conducted and used to calibrate DEM models. Three samples were tested in a multi-stage triaxial test [2] to obtain the mechanical properties of the intact rock. Three other samples were subjected to an injection of a CO2 solution and then to a multi-stage triaxial test. A DEM model with spherical particles, using a modified bonded particle model [3] as contact model was calibrated with the results of the tests performed on the intact samples. A second DEM model was calibrated using the first stage of the triaxial test from the CO2 laboratory altered samples. The other two stages from the multi-stage triaxial test were used to validate the DEM methodology. The laboratory tests showed a significant reduction in the material Young’s modulus, Poisson’s ratio, and strength parameters after CO2 injection. The DEM models could accurately capture the drop in the mechanical parameters obtained by the laboratory.