Simulation of CO2 sequestration in deep geological formations is a multi-disciplinary effort involving the study of multi-phase flow of groundwater and carbon dioxide along with porous medium deformation caused by pore pressure increase. The latter can cause the ground surface to rise because of the reduction of the effective stress in the aquifer and consequent rock expansion. A preliminary analysis of CO2 sequestration in a brackish aquifer between 600 and 800 m below the Venice Lagoon is presented. Using available geological, geophysical, hydrologic, and geomechanical data, and with the aid of advanced numerical models, several scenarios are addressed to investigate the potential of the proposed solution as far as both the CO2 storage and the possible land uplift are concerned. The results show that with the most probable hydrogeological configuration the total amount of CO2 released from nearby thermo-power plants, i.e., 20 Mt/year, can be safely sequestered, with an expected city uplift over 10 years ranging between 7 and 13 cm, depending on well configuration. This would make up for most of the anthropogenic land subsidence experienced by Venice over the last half-century and could offset between 50 and 70 percent of the “acqua alta” that periodically floods Venice. The simulations, however, show a high sensitivity to sand permeability and compressibility, which points to the need for new field investigations before the present preliminary proposal may be turned into an actual feasibility study.