The oxygen isotope composition of 169 whole-rock samples from the world-class LaRonde Penna Au-rich volcanogenic massive sulfide deposit range from 6.5 to 22.0‰. Fractional crystallization from basalt to rhyolite accounts for a variation of approximately 2‰ in primary whole-rock δ18O values. The remaining variance in whole-rock δ18O values found at LaRonde Penna must therefore be ascribed to water-rock exchange with hydrothermal fluids. The metamorphosed, hydrothermally altered host rocks have been subdivided according to mineralogical assemblages, which display weak covariance with δ18O values and whole-rock geochemical alteration indices. Water-rock equilibrium exchange models indicate that the high δ18O values that characterize the LaRonde Penna deposit are compatible with low-temperature (~150ºC) hydrothermal alteration at high water-rock oxygen atomic ratios (1–50). Zones of lower δ18O values stratigraphically beneath the principal ore lens (20 North) indicate local zones of higher temperature hydrothermal alteration. The oxygen isotope composition of the hydrothermal fluid is estimated to have been ~5‰, as a consequence of mixing between seawater (δ18O ~0‰) and a component of magmatic water degassed from the volcanic and intrusive rocks associated with the LaRonde Penna deposit.