The lone pair-pi interaction between H2O and C6F6 was studied using matrix isolation infrared spectroscopy and quantum chemical calculations. Co-deposition of H2O with C6F6 in a nitrogen matrix at 17 K followed by annealing to 30 K, results in the appearance of multiple new peaks in the infrared spectrum that are shifted from the H2O and C6F6 parent absorptions. These peaks only appear when both the H2O and C6F6 are present and have been assigned to distinct structures of a 1:1 H2O center dot C6F6 complex. Similar experiments were performed with D2O and HDO and the corresponding infrared peals for the structures of the D2O center dot C6F6 and HDO:C6F6 complexes have also been observed. Theoretical calculations were performed for the H2O:C6F6 complex using the B3LYP, MP2, and CCSD(T) methods. Geometry optimizations at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ levels of theory located three structural minima, all of which involve the lone pair-pi interaction between the H2O and the C6F6 ring, but with different relative orientations of the H2O and C6F6 subunits. BSSE corrected interaction energies were estimated at the CCSD(T)/aug-cc-pVTZ level and found to be between -11.2 and -12.3 kJ/mol for the three H2O center dot C6F6 structures. Vibrational frequencies for the each of the structures were calculated at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ levels. The frequencies calculated with both methods support the assignments of the observed new peaks in the infrared spectra to the structures of the H2O center dot C6F6 complex; however, the B3LYP calculated frequency shifts were found to be in better quantitative agreement with the experimentally observed frequency shifts.