Understanding the behavior of a clay mineral-rich rock submitted to different physical-chemical perturbations is important for assessing the safety of nuclear waste disposal facilities in the corresponding geological formations. In this work we studied the effect of rock desaturation on the CO2 partial pressure signature of the Callovo-Oxfordian argillite. This integrated study, which combines experiments and geochemical modeling, points out the primary role of capillary forces on the chemical equilibria. In particular, it was possible to model, without any fitting parameters, the experimental decrease of pCO2 as a function of decreasing water content in the argillite. Moreover, this application to a complex natural system is an example of confirmation of the theoretical concepts of geochemistry in capillary contexts and is promising for dealing with other natural and industrial systems.