This research is aimed toward an understanding of the effects of the chemical characteristics and mineral compositions of sandstone and formation water based on saline water-rock-supercritical CO2 interaction simulation experiments. These experiments were conducted to assess whether toxic trace elements could be dissolved and released in formation water from sandstone in a CO2 storage layer after CO2 geological sequestration, thus affecting groundwater quality. The experimental results reveal that the concentrations of Cd and Pb in the water under examination exceeded the national primary drinking standard as a result of saline/fresh water-rock-supercritical CO2 interactions after 40 d of sandstone immersion in saline/fresh water and 20 d of interaction. In addition, the Mn concentration in the saline/fresh water exceeded the national secondary drinking standard after 40 d of sandstone immersion and 20–80 d of interaction. However, Cd, Pb, and Mn were released to a greater extent (in terms of concentration, 2-fold for Cd, 7-fold for Pb, and 1.7-fold for Mn) in the presence of salinity, revealing that salinity may enhance the dissolution of Cd, Pb, and Mn after 20 d of saline water-rock-scCO2 interaction. After a long period of supercritical CO2-sandstone interaction, the trace metals previously mobilized can be immobilized again by an increase in alkalinity due to aragonite dissolution.