The oxidation of alkenes by H2O2 catalyzed by Ti(IV)-containing polyoxometalates (POMs) as models of Ti single-site catalysts has been investigated at DFT level and has been compared with other early transition-metal-substituted polyoxometalates. We have studied in detail the reaction mechanism of the C2H4 epoxidation with H2O2 mediated by two different POMs, the Ti-monosubstituted Keggin-type POM [PTi(OH)W11O39](4-) and the Ti-disubstituted sandwich-type POM[Ti-2(OH)(2)As2W19O67(H2O)](8-). These species exhibit well-defined 6- and 5-coordinated titanium environments. For both species, the reaction proceeds through a two-step mechanism: (i) the Ti-OH groups activate H2O2 with a moderate energy barrier yielding either Ti-hydroperoxo (Ti-IV/OOH) or Ti-peroxo (Ti-IV-OO) intermediate, and (ii) the less stable but more reactive Ti-hydroperoxo species transfers oxygen to alkene to form the epoxide, this latter step being the rate-determining step. The higher activity of the sandwich anion was attributed to the absence of dimer formation, and its higher selectivity to the larger energy cost of homolytic O-O bond breaking in the hydroperoxo intermediate. We also propose several requisites to improve the efficiency of Ti-containing catalysts, including flexible and 5-fold (or lower) coordinated Ti environments, as well as reagent-accessible Ti sites. Calculations on other TM-containing Keggin-type POMs [PTM(OH)W11O39](4-) (TM = Zr(IV), V(V), Nb(V), Mo(VI), W(VI), and Re(VII)) showed that when we move from the left to the right in the periodic table the formation of the epoxide via peroxo intermediate becomes competitive because of the higher mixing between the orbitals of the TM and the O-O unit.