In this study, the impact of salinity and alkalinity on the volumetric deformation of the Opalinus Clay from the lower sandy facies (LSF) of Mont Terri site was investigated. Series of samples were exposed in parallel to alkaline solutions at four different pHs (8.8, 11.5, 12.5 and 13.5) or to saline solutions at three different osmotic suctions (π = 10, 15 and 34 MPa). As a reference, samples were also exposed to synthetic water at pH 7.5 and π = 1 MPa. It was found that the protocol followed above (“parallel testing”) was not suitable for the LSF Opalinus Clay due to the high mineralogy variability. Therefore, a new protocol (“gradual testing”) consisting of gradually exposing the same sample to diferent saline or alkaline solutions was adopted. It was found that the volumetric swelling strain increased with alkalinity and decreased with salinity. In the first case, the acid-base attack resulted in a dispersed structure with higher repulsive forces. Also, the precipitation of new compounds composed of the products of the dissolution of clay minerals and the species present in the alkaline solution contributed to the observed increase in swelling strain. For the saline solutions, the decrease of the thickness of diffuse double layer and the osmotically induced consolidation explained the observed decrease of swelling strain.