The structures and relative stabilities of the complexes formed by uracil and its sulfur derivatives, namely, 2-thio-, 4-thio, and 2,4-dithio-uracil when interacting with Ca²⁺ in the gas phase have been analyzed by means of density functional theory (DFT) calculations carried out at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) level. For uracil and 2,4-dithiouracil, where the two basic sites are the same, Ca²⁺ attachment to the heteroatom at position 4 is preferred. However, for the systems where both types of basic centers, a carbonyl or a thiocarbonyl group, are present, Ca²⁺–oxygen association is favored. The most stable complexes correspond to structures with Ca²⁺ bridging between the heteroatom at position 2 of the 4-enol (or the 4-enethiol) tautomer and the dehydrogenated ring nitrogen, N3. The enhanced stability of these enolic forms is two-fold, on the one hand Ca²⁺ interacts with two basic sites and on the other triggers a significant aromatization of the ring. Besides, Ca²⁺ association has a clear catalytic effect on the tautomerization processes which connect the oxo–thione forms with the enol–enethiol tautomers. Hence, although the enol–enethiol tautomers of uracil and its thio derivatives should not be observed in the gas phase, the corresponding Ca²⁺ complexes are the most stable species and should be accessible, because the tautomerization barriers are smaller than the Ca²⁺ binding energies.