Subducting serpentinized lithosphere has distinct δD and δ18O values compared to normal mantle. Slab-derived fluids that infiltrate the mantle wedge can alter its oxygen and hydrogen isotope composition, raising or lowering the δ18O and δD values depending on the nature of the subducted components. Hydrous minerals in peridotite xenoliths from the Colorado Plateau (southwestern USA) have δD values (up to −33‰) much higher than average mantle (−80‰), but similar to δD values of olivine-hosted melt inclusions within arc basalts, suggesting a slab-derived fluid source. Oxygen isotope ratios of olivine from these xenoliths are similar to average mantle, yet display a strong negative correlation with clinopyroxene Ce/Sm, a proxy of metasomatism. This correlation is most simply explained by metasomatism from fluids derived from the serpentinized portion of the Farallon slab. Although δ18O values of mantle minerals span a narrow range, integration of stable isotope data with other geochemical tracers can provide new constraints on modern and ancient subduction-related processes, potentially providing a method for probing Archean lithospheric mantle for evidence of early subduction.