Isotopic substitutions largely affect the dielectric relaxation dynamics of hydrogen-bonded liquid water; yet, the role of the altered molecular masses and nuclear quantum effects has not been fully established. To disentangle these two effects we study the dielectric relaxation of light (H216O), heavy (D216O) and heavy-oxygen (H218O) water at temperatures ranging from 278 to 338 K. Upon 16O/18O exchange, we find that the relaxation time of the collective orientational relaxation mode of water increases by 4–5%, in quantitative agreement with the enhancement of viscosity. Despite the rotational character of dielectric relaxation, the increase is consistent with a translational mass factor. For H/D substitution, the slow-down of the relaxation time is more pronounced and also shows a strong temperature dependence. In addition to the classical mass factor, the enhancement of the relaxation time for D216O can be described by an apparent temperature shift of 7.2 K relative to H216O, which is higher than the 6.5 K shift reported for viscosity. As this shift accounts for altered zero-point energies, the comparison suggests that the underlying thermally populated states relevant to the activation of viscous flow and dielectric relaxation differ.