The prevention of nonspecific protein adsorption to synthetic materials and devices presents a major design challenge in the biomedical community. While some chemical groups can resist nonspecific protein adsorption from simple solutions for limited contact times, there remains a need for new nonfouling functional groups and surface coatings that prevent protein adsorption from complex media like blood or in harsh environments like seawater. Recent studies of the molecular mechanisms of nonfouling surfaces have identified a strong correlation between surface hydration and resistance to nonspecific protein adsorption. In this work, we describe a simple experimental method for evaluating the intrinsic hydration capacity of model surface coating functional groups based on the partial molal volume at infinite dilution. In order to evaluate a range of hydration capacity and nonfouling performance, solutes were selected from three classes: ethylene glycols, sugar alcohols, and glycine analogues. The number of hydrating water molecules bound to a solute was estimated by comparing the molecular volume at infinite dilution to the solute van der Waals molecular volume. The number of water molecules associated with each solute was further validated by constant pressure and temperature molecular dynamics simulations. Finally, a size-normalized molecular volume was correlated to previously observed protein adsorption experiments to relate the intrinsic hydration capacity of functional groups to their known nonfouling abilities.