Reactions of electronically excited singlet oxygen ( 1 O 2 ) with the radical cations of guanine (9HG •+ ), 9-methylguanine (9MG •+ ), 2′-deoxyguanosine (dGuo •+ ), and guanosine (Guo •+ ) were studied in the gas phase by a combination of guided-ionbeam mass spectrometric measurement of product ions and cross sections as a function of collision energy (E col ) and electronic structure calculations of the reaction potential energy surface (PES) at various levels of theory. No product could be captured in the 1 O 2 reaction with bare 9HG •+ or 9MG •+ , because energized products decayed rapidly to reactants before being detected. To overcome this unfavorable kinetics, monohydrated 9HG •+ •H 2 O and 9MG •+ •H 2 O were used as reactant ions, of which the peroxide product ions were stabilized by energy relaxation via elimination of the water ligand. Reaction cross sections for 9HG •+ •H 2 O and 9MG •+ • H 2 O decrease with increasing E col , becoming negligible above 0.6 eV. This indicates that the reactions are exothermic with no barriers above reactants and the heat of formation of the products is sufficiently large to overcome their water ligand elimination energy (0.7 eV). Peroxide product ions were also detected in the 1 O 2 reactions with unhydrated dGuo •+ and Guo •+ , in which intramolecular vibrational redistribution was able to stabilize oxidation products. 9MG •+ was utilized as a model system to explore the reaction PES for the initial 1 O 2 addition to the guanine radical cation. Calculations were carried out using single-reference ωB97XD, RI-MP2, and DLPNO-CCSD(T) and multireference CASSCF and CASPT2. Although the same PES profile was obtained at different levels of theory, the energies of the mixed open-and closed-shell 1 O 2 reactant and the open-shell reaction intermediates, transition states, and products are sensitive to the theories. By taking into account both static and dynamic electron correlations, the CASPT2 PES has provided the best agreement with the experimentally measured reaction thermodynamics and predicted 8peroxide as the most probable initial oxidation product of the guanine radical cation.