The interactions between a nitrile rubber O-ring model polymer and selected fuel species were investigated using one of the hybrid density functional theories (DFT), B3LYP. The primary objective of this study was to examine whether theoretical investigation can be used as a potential tool to predict the intensity of the polymer-fuel species interaction, namely, swelling, and if so, which calculated properties have a strong correlation with experimentally observed swelling behavior. The fuel species investigated were ethylbenzene, phenol, methylphenol, phenylmethanol, phenylethanol, phenylbutanol, 1-butanol, 1-hexanol, cyclohexanol, and di- and triethylene glycol monomethyl ether (diEGME and triEGME, respectively). The model polymer created to represent the nitrile rubber O-ring was cis-butadiene-acrylonitrile-trans-butadiene (cis-C4H7-CH2CHCN-trans-C4H7). The properties investigated were charge distribution, intermolecular distances, binding energies, and vibrational frequency shifts corresponding to the cyano group stretching mode of the model polymers because of the interaction. Some of the cyano group vibrational frequency shifts were compared to an experimentally observed infrared absorption peak shift associated with the nitrile rubber cyano group because of polymer-fuel species interactions. There is a strong correlation among calculated intermolecular distances, binding energies, and frequency shifts. The order of interaction intensities between polymer and fuel species based on the calculated parameters is also consistent with the order of interaction intensities based on the experimentally derived partition and swelling coefficients. The B3LYP/6-311G(d,p) derived vibrational frequency shift associated with the cyano group stretching mode showed good agreement with the experimentally measured adsorption peak shift.