Tautomerism and proton transfer in 6-selenoguanine (6SeG) have been investigated using high level ab initio calculations. Full geometry optimizations were carried out in the gas phase at the HF and MP2 levels using the 6-31G(d,p) basis set. Furthermore, the single point energies were evaluated using larger basis sets augmented with diffuse and polarization functions. At all applied levels of theory, the N-7 protonated form is shown to be the most stable one in the gas phase and is 3.1 kcal/mol more stable than the N-9 protonated tautomer at the MP2/6-311++G(d,p)//MP2/6-31G(d,p) level. However, aqueous solvation studies using the SCI-PCM continuum models show a different trend for energetic preference for selenoguanines. Estimated free energies of tautomerization in an aqueous medium indicate that the N9 protonated form is more stable than the N7 protonated form although the energies of these two tautomers are very close. Our calculations suggest that the Se-6 protonated form of N-9-selenoguanine is the most hydrated one while the selenoic form of N-9-selenoguanine is the least hydrated one. The following stability order may be established for 6-selenoguanine in the gas phase, 6SeG4 > 6SeG3 > 6SeG2 > GSeG1 > 6SeG5, while in an aqueous solution, a stability order as such is established, GSeG1 > 6SeG4, 6SeG3 > 6SeG2 > 6SeG5. The proton transfer from the N-1 to the Se-6 site involves an energy barrier of about 39 kcal/mol for the N-9 protonated tautomer and 46 kcal/mol for the N-7 protonated tautomer at the HF level and 31.8 and 36.6 kcal/mol, respectively, at the MP2/6-311++G(d,p)//MP2/6-31G(d,p) level.