Jadeitites and albitites from the Motagua Valley, Guatemala, are high-pressure–low-temperature metasomatic rocks that occur as tectonic inclusions in serpentinite-matrix melange. Metasomatism was driven by a fluid with a δ18OH2O value of 6‰, and a δDH2O value that is high in comparison with metamorphic fluids at other high-pressure–low-temperature localities of similar grade. We infer that the fluid was originally seawater that was entrained during subduction either as mineral-bound H2O or as free pore waters. The fluid drove serpentinization reactions in ultramafic rocks, possibly leading to deuterium enrichment of H2O, prior to forming the jadeitites and albitites at a depth of 29 ± 11 km. There are isotopic and fluid-inclusion similarities to rodingites, which are Ca-rich metasomatites found at other serpentinite localities. Our results suggest that the serpentinization process, whether it occurs within subduction zones or on the flanks of oceanic spreading ridges, may produce residual fluids that are H2O rich, have 1–8 wt% equivalent NaCl, and have high, perhaps seawater-like, δD values.