Investigating proteins with techniques such as NMR or neutron scattering frequently requires the partial or complete substitution of D2O for H2O as a solvent, often tacitly assuming that such a solvent substitution does not significantly alter the properties of the protein. Here, we report a systematic investigation of the solvent isotope effect on the phase diagram of the lens protein γB-crystallin in aqueous solution as a model system exhibiting liquid-liquid phase separation. We demonstrate that the observed strong variation of the critical temperature Tc can be described by the extended law of corresponding states for all H2O/D2O ratios, where scaling of the temperature by Tc or the reduced second virial coefficient accurately reproduces the binodal, spinodal, and osmotic compressibility. These findings highlight the impact of H2O/D2O substitution on γB-crystallin properties and warrant further investigations into the universality of this phenomenon and its underlying mechanisms.