The free energies of mixing a series of water-soluble polymers with cellulose were calculated using the UNIFAC (universal functional group activity coefficients) algorithm, and the results were correlated with measurements of polymer/cellulose adhesion. The more negative the minimum free energy of mixing, the greater the measured adhesion. Adhesion was quantified by single-lap shear test in which regenerated cellulose films were laminated with aqueous polymer. The results are relevant to the use of adsorbed water-borne polymers to strengthen cellulose fiber-fiber bonds in paper. The calculations did not anticipate the exceptional strength-enhancing properties of carboxymethyl cellulose, nor did they predict molecular-weight effects. Nevertheless, the approach may have utility as a general tool to relate polymer chemistry to adhesion performance.