Chlorine isotope compositions of high-pressure (∼2.3 GPa) serpentinite, rodingite, and hydrothermally altered oceanic crust (AOC) differ significantly from high- and ultrahigh-pressure (> 3.2 GPa) metasedimentary rocks in the Aosta region, Italy. Texturally early serpentinites, rodingites, and AOC have bulk δ37Cl values indistinguishable from those of modern seafloor analogues (δ37Cl = −1.0 to +1.0‰). In contrast, serpentinites and AOC samples that recrystallized during exhumation have low δ37Cl values (−2.7 to −0.5‰); 37Cl depletion correlates with progressive changes in bulk chemistry. HP/UHP metasediments have low δ37Cl values (median = −2.5‰) that differ statistically from modern marine sediments (median = −0.6‰). Cl in metasedimentary rocks is concentrated in texturally early minerals, indicating modification of seafloor compositions early in the subduction history. The data constrain fluid sources during both subduction and exhumation-related phases of fluid-rock interaction: (1) marine sediments at the top of the downgoing plate likely interacted with isotopically light pore fluids from the accretionary wedge in the early stages of subduction. (2) No pervasive interaction with externally derived fluid occurred during subsequent subduction to the maximum depths of burial. (3) Localized mixing between serpentinites and fluids released by previously isotopically modified metasediments occurred during exhumation in the subduction channel. Most samples, however, preserved protolith signatures during subduction to near-arc depths.