SelW, a protein containing a selenocysteine (Sec) in a conserved Cys-X-X-Sec motif, has been suggested to have an antioxidant role in cell metabolism. SelW is known to specifically interact with different isoforms of 14-3-3 proteins. The latter are involved in several cellular processes such as regulation of the cell cycle, metabolism control, apoptosis, protein trafficking, and gene transcription. 14-3-3 proteins feature a conserved solvent-exposed cysteine residue, in a surface environment prone to induce chemical modifications of the thiol functionality following oxidative stress. The structures of 12 homologous complexes between SelW and 14-3-3 were calculated using sequential alignments, molecular modeling, and docking algorithms guided by known experimental NMR data. These structures reveal the viability of a protein complex in which the conserved Sec residue on SelW approaches the conserved exposed Cys on 14-3-3, making a plausible Sec-Se-S-Cys bond. On the basis of the structural information derived from these calculations, we propose a working hypothesis that entails a role for SelW as a physiological partner of 14-3-3 proteins, able to facilitate a redox-based regulation mechanism.