The Patterson Lake corridor (PLC), located on the southwestern margin of the Athabasca Basin, contains several basement-hosted uranium deposits that formed via protracted, structurally controlled fluid-rock interactions. Using multiple generations of pyrite grains (pre-, syn- and post-mineralization) from the Triple R deposit, in-situ iron isotopic analyses revealed large intra-sample and -grain variations (δ56Fe values ranging from -2.21 to +1.67 ‰) whereas sulfur isotopes yielded minor variations (δ34S values ranging from -4.44 to + 5.3 ‰) relative to natural isotopic variations for both elements. The wide range in δ56Fe values supports textural and chemical evidence that fluctuating oxidation states and chemistry in the fault zone fluids caused multiple generations of pyrite oxidation and precipitation. Sulfur isotope data from shallower mineralized zones show a slight enrichment in heavier isotopes consistent with limited Rayleigh fractionation. However, when coupled with iron isotope data, the overall dataset supports a sulfur-rich, open system wherein heat from intrusions at depth and fault movements drove sulfur-rich fluids upwards, causing precipitation of pre-mineralization pyrite and graphite. During fault reactivation, fluid pressure fluctuations between hydrostatic and sub-hydrostatic regimes drew oxidizing, uranium-bearing, basinal brines down into the basement to react with sulfides in the host rocks and deeply sourced, H2S-bearing reducing fluids. These redox reactions and fluid mixing resulted in precipitation of uraninite and syn-mineralization pyrite. These results further support the importance of structural control, repeated faulting and thermal anomalies in the basement for mineralization, necessitating re-examination of the current exploration model for unconformity-related uranium deposits.Thematic collection: This article is part of the Uranium Fluid Pathways collection available at: https://www.lyellcollection.org/cc/uranium-fluid-pathwaysSupplementary material:https://doi.org/10.6084/m9.figshare.c.6026621