The influence of enyne substituents in the product selectivity of the Ring-Closing Enyne Methathesis (RCEYM) catalyzed by the most common mesithyl-containing second-generation Ru-based Grubbs type complexes has been studied by means of density functional theory (DFT, B3LYP-D) calculations. For this, we have computed the energetics of the three proposed mechanism (ene-then-yne; exo-yne-then-ene, and endo-yne-then-ene) of a series of 11 different enynes that share the 1-allyloxyprop-2-yne skeleton. Three different substitutions have been taken into account: the alkyne fragment terminal position, the propargylic carbon, and the internal carbon of the alkene fragment. For the first two substitution positions, models including hypothetical electron-donor and electron-withdrawing substituents have been considered. Present calculations show that nonproductive pathways leading to catalyst deactivation are competitive with the catalytic cycle when nonsubstituted enynes are made to react. Nevertheless, these nonproductive pathways are prevented by the addition of small substituents in the alkene moiety and in the terminal position of the alkyne. In these cases, a methyl group in the alkene moiety prevents to a large extent the ene-then-yne route, and thus, the reaction preferentially proceeds through the yne-then-ene mechanism. This leads to the potential formation of both the exo and the endo products. Moreover, when the ene-then-yne route is prevented, the preference for one or the other product seems to depend on not only the steric hindrance of the substituents. In this way, enynes with terminal alkyne fragments proceed preferentially through the exo route. However, when the alkyne is internal, the two carbons of the alkyne fragment have similar atomic charges, and the two routes become competitive. Therefore, both exo- and endo- products can be formed, as seen experimentally.