Caprocks with significant clay content are candidate seal layers for CO2 geological storage. Changes in electrical and capillary forces are expected when CO2 invades the water saturated pore space. Sedimentation experiments conducted to explore the response of kaolinite and montmorillonite to deionized water, brine, heptane, liquid CO2 and supercritical CO2 show that both montmorillonite and kaolinite aggregate when submerged in CO2 and the final porosity in CO2 is smaller than in brine. Differences in dielectric properties between CO2 and water, and ensuing implications on van der Waals attraction and double layer repulsion explain the observed phenomena. On the other hand, capillary effects induced by the water–CO2 interface are corroborated by clay–water paste desiccation experiments conducted using supercritical CO2: water dissolution into the surrounding CO2 causes suction and capillary contraction, the invasion of the CO2–water interface into the sediment, and the formation of desiccation cracks. Volume contraction and crack initiation are consistent with the sediment response within an effective stress framework. Altered electrical forces and emergent capillary forces lead to coupled chemo-hydromechanical phenomena in seal layers that could facilitate CO2 breakthrough and advection through high porosity caprocks; related phenomena are identified in the reservoir rock. Additional studies are needed to further assess coupled phenomena when the interparticle distance is a few monolayers of water.