Abstract Fluid-induced alteration of rocks and mineral-based materials often starts at confined mineral interfaces where nm-thick water films can persist even at high overburden pressures and at low vapor pressures. These films enable transport of reactants and affect forces acting between mineral surfaces. However, the feedback between the surface forces and reactivity of confined solids is not fully understood. We used the surface forces apparatus (SFA) to follow surface reactivity in confinement and measure nm-range forces between two rough calcite surfaces in NaCl, CaCl2, or MgCl2 solutions with ionic strength of 0.01, 0.1 or 1 M. We observed long-range repulsion that could not be explained by changes in calcite surface roughness, surface damage, or by electrostatic or hydration repulsion, but was correlated with precipitation events which started at µm-thick separations. We observed a submicron-sized precipitate that formed in the confined solution. This liquid-like viscous precipitate did not undergo any spontaneous ripening into larger crystals, which suggested that confinement prevented its dehydration. Nucleation was significantly postponed in the presence of Mg2+. The long-range repulsion generated by nucleation between confined mineral surfaces can have a crucial influence on evolution of the microstructure and therefore the macroscopic strength of rocks and materials.