Interactions between injected CO2, brine, and rock during CO2 sequestration in deep saline aquifers alter their natural hydro-mechanical properties, affecting the safety, and efficiency of the sequestration process. This study aims to identify such interaction-induced mineralogical changes in aquifers, and in particular their impact on the reservoir rock" s flow characteristics. Sandstone samples were first exposed for 1.5 years to a mixture of brine and super-critical CO2 (scCO2), then tested to determine their altered geochemical and mineralogical properties. Changes caused uniquely by CO2 were identified by comparison with samples exposed over a similar period to either plain brine or brine saturated with N 2. The results show that long-term reaction with CO2 causes a significant pH drop in the saline pore fluid, clearly due to carbonic acid (as dissolved CO2) in the brine. Free H + ions released into the pore fluid alter the mineralogical structure of the rock formation, through the dissolution of minerals such as calcite, siderite, barite, and quartz. Long-term CO2 injection also creates a significant CO2 drying-out effect and crystals of salt (NaCl) precipitate in the system, further changing the pore structure. Such mineralogical alterations significantly affect the saline aquifer permeability, with important practical consequences for the sequestration process.