A good understanding of CO₂–brine–rock interactions that cause microscale damage to the microstructure of sandstone, affecting pore fluid transport and reservoir stability, is important for studying storage efficiency during CO₂ storage. In this study, the equipment is first designed to saturate rock samples using CO₂–brine under in situ conditions and then the homogeneous and heterogeneous sandstone samples are saturated for 30 days with and without the confining pressure (20 MPa). Through scanning electron microscopy (SEM) observation and analysis, it is found that the confining pressure reduces the degree of damage in various scales from micrometer to millimeter, such as reducing the mineral dissolution, decreasing the induced swelling of the bedding planes, and causing some pores to collapse. The nuclear magnetic resonance results show that the change in porosity is mainly caused by the increase in the number of relatively small-sized (characterized in terms of fluid relaxation time T₂ < 10^–3 s) pores after CO₂–brine saturation. In addition, the alterations of the pore system in homogeneous and heterogeneous sandstones are different, such as a larger increase in the porosity of homogeneous sandstone (by 5.29%). In heterogeneous sandstone, the effect of mineral dissolution induced by chemical reactions on damaging the microstructure is more obvious than mineral swelling. In addition, it is found that the CO₂–brine saturation decreases the fractal dimension of the sandstone by nearly 2%, increasing the pore connectivity. This study is helpful for understanding the evolution of the sandstone microstructure under geological conditions during the long-term CO₂ storage process.