The effect of the chemical composition of regenerated cellulose solids on surface energy was studied by inverse gas chromatography (IGC). This was to probe a possible relationship between the ability of the cellulose surface to interact with other phases through van der Waals forces and its bonding potential. A model consisting of amorphous cellulose spheres ("beads") was used to eliminate all effects of morphology and geometry. The surface of the beads was modified by chemical reaction of the hydroxyl groups of cellulose. A thin layer of cellulose derivative, such as cellulose trifluoroethoxyacetate (CW-TFEA), cellulose laurate (CW-LA), or directly fluorinated cellulose (CW-F), was produced on the bead surface. The surface properties of the cellulose beads were fully characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and nitrogen adsorption. IGC was performed using the adsorption of two kinds of probes: alkanes to measure the dispersive component of the surface energy (γsd), and acid/base probes to quantify the specific adsorption enthalpy (ΔHsp). The dispersive component of the surface energy of cellulose was found to depend mostly on the presence and concentration of free hydroxyl groups on the surface. At low degrees of substitution (DS < 1), how these OH groups were replaced by modification, whether by fatty acid type substituents or by fluorine-containing groups, was essentially irrelevant for surface energies. The dispersive component of the surface energy (γsd) declined with DS almost irrespective of substituent type. The surface of cellulose was found to be highly acidic, and this was attributed mainly to the presence of hydroxyl groups.