Understanding the physical and chemical behaviour of a sedimentary sequence during post-depositional fluid flow is of prime importance in evaluating its potential in the context of a nuclear waste deep repository. The Cretaceous siltstones of the Marcoule area (Gard, south-eastern France), investigated by ANDRA (French nuclear waste management agency) as a potential site for such a storage facility but finally not selected for the construction of an underground laboratory, are intersected by two major faults which show evidence of fluid circulation through the sequence postdating deposition. Late-stage fluid circulation induced secondary mineral crystallisation (calcite, celestite, pyrite, and barite, referred here as “epigenetic” as opposed to paragenetically earlier calcite and pyrite development during burial and referred here as “diagenetic”). These epigenetic phases occur both in the fault and in sub-perpendicular fractures in the surrounding siltstones. Clay minerals appear to be unaffected by this fluid circulation, and both mineralogical and isotopic (K–Ar) results argue in favour of simple physical reworking of the surrounding clay material, without significant mobilization of the major and trace elements. Rare earth elements, which might be considered as natural analogues of actinides, exhibit any variation in content between fault and siltstones clay-size fractions. In agreement with mineralogical and isotopic results, this behaviour might traduce that REE remained bound to the clay minerals and were not significantly remobilized into other mineral phases. The effect of the fluid interaction can only be deduced from increase in Sr, Ba and Pb contents in the finest clay size fractions. These elements are probably incorporated into mineral phases associated with the clay particles. They appear to be of local origin, as suggested by the Sr-isotope ratio of the epigenetic calcites close to that of diagenetic calcite. A difference of Pb-isotope composition between diagenetic (formed in the matrix during early and burial diagenesis) and epigenetic (precipitated in the gouge during late-stage fluid flow) pyrite is thought to reflect the Pb-isotope evolution over time in the siltstones until the formation of pyrite in the gouge. Assuming that the diagenetic pyrite formed during very early diagenesis in the sequence (c. 97–98 Ma based on glauconite dating [Rousset, D., Leclerc, S., Clauer, N., Lancelot, J., Cathelineau, M., Aranyossy, J.F., 2004. Age and origin of Albian glauconites and associated clay minerals inferred from a detailed geochemical analysis. Journal of Sedimentary Research 74, 631–642.]), a modelled-evolution of the Pb-isotope composition leads to an estimate of the time elapsed between diagenesis and fluid flow of some 60 Ma. Consequently, fluid circulation which precipitated pyrite could have occurred 39 ± 7 Ma ago, during the Pyrenean thrusting.