The hydration of bovine and genetically variable caprine caseins in D2O solutions of sucrose and lactose was investigated by oxygen-17 NMR and fitted by nonlinear regression analysis. A charge-charge interaction model was employed to analyze the transverse relaxation (1/T2) data. Lactose caused increased hydration of the bovine casein and the caprine casein naturally low in αs1-casein, whereas sucrose led to increased hydration of the caprine casein naturally high in αs1-casein. At pD 7.20 and 21 °C the effect of charge-charge repulsive interactions on the native caseins generally leads to decreased protein stability in bovine and caprine caseins. However, addition of sugars causes stronger (attractive) interactions yielding more stable casein complexes with increased hydration. The calculated preferential binding term -(∂gs/∂gp) for casein mixtures suggests that sucrose and lactose are "preferentially" excluded from these milk proteins, yielding greater access to much of the aqueous compartment. This is consistent with the view that sugars lead to the stabilization of proteins in nonfrozen, aqueous systems.