High-level ab initio calculations have been used to determine the oxidation and reduction potentials of a large number of nitroxides including derivatives of piperidine, pyrrolidine, isoindoline, and azaphenalene, substituted with COOH, NH2, NH3+, OCH3, OH, and NO2 groups, with a view to (a) identifying a low-cost theoretical procedures for the determination of electrode potentials of nitroxides and (b) studying the effect of substituents on these systems. Accurate oxidation and reduction potentials to within 40 mV (3.9 kJ mol(-1)) of experimental values were found using G3(MP2)-RAD//B3-LYP/6-31G(d) gas-phase energies and PCM solvation calculations at the B3-LYP/6-31G(d) level. For larger systems, an ONIOM method in which G3(MP2)-RAD calculations for the core are combined with lower-cost RMP2/6-311+G(3df,2p) calculations for the full system, was able to approximate G3(MP2)-RAD values (to within 1.6 kJ mol(-1)) at a fraction of the computational cost. The overall ring structure has more effect on the electrode potentials than the inclusion of substituents. Azaphenalene derivatives display the lowest oxidation potentials and least negative reduction potentials and are thus the most promising target to function as antioxidants in biological systems. Piperidine and pyrrolidine derivatives have intermediate oxidation potentials but on average pyrrolidine derivatives display more negative reduction potentials. Isoindoline derivatives show higher oxidation potentials and more negative reduction potentials. Within a ring, the substituents have a relatively small effect with electron donating groups such as amino and hydroxy groups stabilizing the oxidized species and electron withdrawing groups such as carboxy groups stabilizing the reduced species, as expected.