The Opalinus Clay (OPA) is a clay-rich formation considered as a potential host rock for radioactive waste repositories and as a caprock for carbon storage in Switzerland. Its very low permeability (10 −19 to 10 −21 m 2) makes it a potential sealing horizon, however the presence of faults that may be activated during the lifetime of a repository project can compromise the longterm hydrological confinement, and lead to mechanical instability. Here, we have performed laboratory experiments to test the effect of relative humidity (RH), grain size (g.s.) and normal stress on rate-and-state frictional properties and stability of fault laboratory analogues corresponding to powders of OPA shaly facies. The sifted host rock powders at different grain size fractions (<63 μm and 63 < g.s. < 125 μm), at room (∼25 per cent) and 100 per cent humidity, were slid in double-direct shear configuration, under different normal stresses (5-70 MPa). We observe that peak friction, μ peak and steady-state friction, μ ss , depend on water vapour content and applied normal stress. Increasing relative humidity from ∼25 per cent RH (room humidity) to 100 per cent RH causes a decrease of frictional coefficient from 0.41 to 0.35. The analysis of velocity-steps in the light of rate-and-state friction framework shows that the stability parameter (a-b) is always positive (velocity-strengthening), and it increases with increasing sliding velocity and humidity. The dependence of (a-b) on slip rate is lost as normal stress increases, for each humidity condition. By monitoring the variations of the layer thickness during the velocity steps, we observe that dilation (h) is directly proportional to the sliding velocity, decreases with normal stress and is unaffected by humidity. Microstructural analysis shows that most of the deformation is accommodated within B-shear zones, and the increase of normal stress (σ n) promotes the transition from strain localization and grain size reduction to distributed deformation on a well-developed phyllosilicate network. These results suggest that: (1) the progressive loss of velocity dependence of frictional stability parameter (a-b) at σ n > 35 MPa is dictated by a transition from localized to distributed deformation and (2) water vapour content does not affect the deformation mechanisms and dilation, whereas it decreases steady-state friction (μ ss), and enhances fault stability.