We present a structural, microstructural, and stable isotope study of a calcite vein mesh within the Cretaceous Natih Formation in the Oman Mountains to explore changes in fluid pathways during vein formation. Stage 1 veins form a mesh of steeply dipping crack-seal extension veins confined to a 3.5-m-thick stratigraphic interval. Different strike orientations of Stage 1 veins show mutually crosscutting relationships. Stage 2 veins occur in the dilatant parts of a younger normal fault interpreted to penetrate the stratigraphy below. The δ18O composition of the host rock ranges from 21.8‰ to 23.7‰. The δ13C composition ranges from 1.5‰ to 2.3‰. This range is consistent with regionally developed diagenetic alteration at top of the Natih Formation. The δ18O composition of vein calcite varies from 22.5‰ to 26.2‰, whereas δ13C composition ranges from −0.8‰ to 2.1‰. A first trend observed in Stage 1 veins involves a decrease of δ13C to compositions nearly 1.3‰ lower than the host rock, whereas δ18O remains constant. A second trend observed in Stage 2 calcite has δ18O values up to 3.3‰ higher than the host rock, whereas the δ13C composition is similar. Stable isotope data and microstructures indicate an episodic flow regime for both stages. During Stage 1, formation of a stratabound vein mesh involved bedding-parallel flow, under near-lithostatic fluid pressures. The 18O fluid composition was host rock-buffered, whereas 13C composition was relatively depleted. This may reflect reaction of low 13C CO2 derived by fluid interaction with organic matter in the limestones. Stage 2 vein formation is associated with fault-controlled fluid flow accessing fluids in equilibrium with limestones about 50 m beneath. We highlight how evolution of effective stress states and the growth of faults influence the hydraulic connectivity in fracture networks and we demonstrate the value of stable isotopes in tracking changes in fluid pathways.