Serpentinization is a ubiquitous hydrothermal alteration of ultramafic rocks. In the Ronda Massif (Andalusia, Spain), which represents the largest body of subcontinental peridotite exposed at the Earth surface, most studies focused on high-temperature deformation and petrology of mantle rocks. Serpentinization remains poorly constrained. Petro-structural and O and H isotope investigations allow us to identify three successive stages of serpentinization. The first stage of serpentinization is characterized by a widespread lizardite mesh-texture. The extent of serpentinization indicates a regional gradient, with a low proportion of serpentine (around 15 %) in the core of the Sierra Bermeja Massif. The second stage corresponds to highly localized serpentinization, characterized by the presence of lizardite, bastite and high content of magnetite. The third stage was intimately associated with brittle deformation, consisting of fibrous veins and a coating network within cataclastic shear zones. Structural analysis of shear veins of the third serpentinization stage enables identification of a regional syn-serpentinization extensional deformation that corresponded to a multi-directional horizontal stretching and a vertical shortening direction (i.e., flattening). All stages of serpentinization display comparable isotopic compositions, with the mean of δ 18O values at ~ +5.0 ‰ and δD at~ −80.5 ‰, suggesting that the two last stages occurred under conditions of fluid-rock interactions that preserved the compositions acquired during stage 1. The fluid source for this stage 1 was likely deeply seated, with a possible contribution of meteoric-derived fluids. Stage 3 serpentinization occurred at 170 ± 50 °C based on magnetite-serpentine isotopic equilibrium. We propose a model of continuous serpentinization that occurred during the rapid exhumation of the Ronda Massif during the Early Miocene period. The syn-serpentinization extensional brittle deformation we document may be compatible either with orogenic thickening (i.e., syn-thrusting) or with early post-thickening collapse.