<p>Although the relative energies of the various tautomers of cytosine and 5-chlorocytosine have been studied in detail, little is known about the relative energies of the <i>N</i>-chlorinated isomers of cytosine. <i>N</i>-chlorination of cytosine is known to occur when cytosine is exposed to hypochlorous acid, a potent oxidant that is formed during the inflammatory process, and is presumed to have consequences concerning, for example, the structural integrity of DNA and RNA. In this study, the high-level G4(MP2) thermochemical protocol has been employed in studying the relative gas-phase free energies of thirty isomers that may be formed upon N-chlorination of cytosine. Using free energy of solvation corrections obtained by way of continuum models (CPCM and SMD), an approximation of the effect of aqueous solvation on the relative energies of the isomers has also been taken into account. In both the gas- and aqueous-phases, the lowest energy isomer is an exocyclic <i>N</i>-chloroimino derivative.</p>