Unambiguous evidence for the engagement of CF3 group in N-H···F-C hydrogen bond in a low polarity solvent, the first observation of its kind, is reported. The presence of such weak molecular interactions in the solution state is convincingly established by one and two-dimensional 1H, 19F, and natural abundant 15N NMR spectroscopic studies. The strong and direct evidence is derived by the observation of through-space couplings, such as, 1hJFH, 1hJFN, and 2hJFF, where the spin polarization is transmitted through hydrogen bond. In an interesting example of a molecule containing two CF 3 groups getting simultaneously involved in hydrogen bond, where hydrogen bond mediated couplings are not reflected in the NMR spectrum, 19F-19F NOESY experiment yielded confirmatory evidence. Significant deviations in the strengths of 1JNH, variable temperature, and the solvent induced perturbations yielded additional support. The NMR results are corroborated by both DFT calculations and MD simulations, where the quantitative information on different ways of involvement of fluorine in two and three centered hydrogen bonds, their percentage of occurrences, and geometries have been obtained. The hydrogen bond interaction energies have also been calculated. © 2013 American Chemical Society.