The iron mine of Tamra (Nefza District, NW Tunisia) is a 50 m thick Upper Mio-Pliocene sedimentary series impregnated by Fe-Mn oxides associated with white clay lenses with high halloysite and kaolinite content. This mineralization results from i) synsedimentary weathering/pedogenesis, and ii) mixing surface water and regional hydrothermal fluids. The oxygen and hydrogen isotope composition of halloysite-kaolinite and goethite-hematite is examined in order to provide new insights into the ore formation. This study concludes that halloysite-kaolinite was not equilibrated only with meteoric fluids: the δ 18O values have a range towards high values that are not consistent with weathering conditions for their formation and/or during their subsequent alteration. The δD and δ 18O values of goethite lead to the same conclusion. The stable isotope compositions could be related to fluid-rock interaction with the underlying marls (and/or skarns), providing relatively high δ 18O values to the fluids responsible for the white clay formation. This model also shows that the Pb-isotope compositions of halloysite-kaolinite are explained by a felsic and a carbonated end-member, similar to other ore deposits (IOCG and Sedex) of the vicinity. Several factors should be considered for the precipitation of halloysite-kaolinite and/or destabilization of primary clays in the Tamra ore, i.e. mixing of deep hot saline fluids, related to a thermally driven circulation, and meteoric waters. This hydrothermal contribution postdates the main synsedimentary weathering/pedogenetic Fe-enrichment and may be related to late Fe, Mn, Pb, Zn and As inputs of the Fe-Mn oxides.