Subduction zone metasomatism is critical for Earth's material exchanges, yet the details of slab dehydration, particularly deserpentinization beneath fore-arcs, remain poorly understood. Here, we present Sr–Mg–Ca isotopic data for Purang rodingites from the western Yarlung Zangbo suture zone (YZSZ), a remnant of the Neo-Tethys Ocean that was subducted during the collision between the Indian and Eurasian Plates. The rodingites, occurring as centimeter- to meter-sized veins and blocks in serpentinized harburgite, are dominated by amphibolite- to greenschist-facies minerals like tremolite, magnesiohornblende, and chlorite. Their cumulate textures and rare earth element patterns resemble troctolite or gabbronorite, presumably formed beneath a seafloor spreading center. The rodingites are enriched in large ion lithophile elements and depleted in high field strength elements, with higher Sr/Nb and Ba/La and lower Nb/U and Ce/Pb ratios than mid-ocean ridge basalts (MORB) and rodingites formed through seawater or serpentinizing fluid alteration of MORB-like protoliths. They also exhibit higher initial 87Sr/86Sr ratios (0.7067–0.7075) and elevated δ26Mg values (−0.22 ± 0.07 ‰ to −0.13 ± 0.02 ‰) compared to unaltered oceanic basalts, while their δ44/40Ca values (0.72 ± 0.02 ‰ to 0.87 ± 0.03 ‰) remain similar to MORB. These signatures point to a metasomatic process beyond seafloor alteration, suggesting modification of a MOR-derived protolith in the fore-arc mantle at slab depths of <40 km, driven by Sr- and Mg-rich fluids from clay-rich sediments and serpentinitized mantle. The measured Sr, Mg and Ca isotope compositions can be reproduced by mixing a MORB-like protolith with hybrid fluids derived from varying proportions of sedimentary clays and serpentinitized peridotite. Combined with previous studies on YZSZ metamorphic soles, we propose that this fore-arc metasomatism occurred during the early Cretaceous, concurrent with the incipient subduction of the Neo-Tethys oceanic rocks. These results highlight the significance of deserpentinization at shallow fore-arc mantle settings during subduction initiation, suggesting that slab dehydration is more complex than previously recognized.