Cellulose (CE) was cross-linked with epichlorohydrin (EPI) at variable compositions, and the fractionation properties were investigated in binary water−ethanol (W−E) solutions, including the pure solvent systems. The relative uptake of each solvent was measured using quantitative 1 H nuclear magnetic resonance (qNMR) spectroscopy. This study highlights the utility of qNMR as a rapid screening method for estimation of solvent selective fractionation in binary mixtures. The uptake properties of CE−EPI cross-linked polymers with ethanol and water were well-described using the Sips isotherm model. Modeling shows that the monolayer surface coverage (Q m ) of ethanol and water onto the polymer materials covers a range (1.13−2.44 g/g) of values with heterogeneous adsorption behavior, in agreement with the Sips exponential fitting parameter (n s ≠ 1). The CE−EPI adsorbents display unique fractionation with water and ethanol from binary solutions, as evidenced by the relative selectivity (R selectivity ) value in binary W−E solvent systems. The R selectivity [Q m (W)/Q m (E)] values at saturative conditions varied (from 1.10 to 2.03) and further illustrate that CE materials display molecular selective solvent fractionation in binary W−E solutions. This study provides a greater molecular level understanding for the adsorptive uptake properties of CE that are relevant to developing CE-based adsorbent technology for the fractionation of biofuels and related chemical separations.