We study cuprates within the dynamical cluster approximation and find that the pseudogap displays an isotope effect of the same sign as observed experimentally. Notwithstanding the nonphononic origin of the pseudogap, the interplay between electronic repulsion and retarded phonon-mediated attraction gives rise to an isotope dependence of the antinodal spectra. Due to the strong momentum differentiation, such an interplay is highly nontrivial and leads to the simultaneous presence of heavier quasiparticles along the nodal direction. We predict an isotope effect in electron-doped materials.Copper-oxide superconductors are characterized by the highest superconducting transition temperatures ever measured and, 25 years after their discovery, the pairing mechanism, to the best of our knowledge, has not yet been clarified. However, this is probably not the main reason why these materials are so intriguing. Indeed, due to the complex interplay between their electronic, magnetic, and lattice degrees of freedom, we still have a very incomplete understanding even of their normal (nonsuperconducting) phase. The most well-known anomaly characterizing the cuprates at small values of doping is the presence of a pseudogap. Using the language of angular-resolved photoemission spectroscopy, the pseudogap is a strong suppression of the photoemission signal in selected parts of the Brillouin zone (BZ), occurring below a characteristic temperature called T * . This phenomenon is believed to be so relevant that any complete theory of cuprates should explain it.Differently from the superconducting transition temperature T c , T * displays a quite marked isotope effect characterized by a negative coefficient, i.e., it increases upon substituting oxygen or copper atoms with correspondingly heavier isotopes. 1-4 This represents an unusual dependence, having conventional BCS theory in mind. Some possible scenarios for its explanation have been proposed: Assuming that the pairing in cuprates is directly mediated by phonons 5 so that the pseudogap is associated to the binding of two polarons with no long-range phase coherence, Ranninger calculated the isotope shift of T * and found good qualitative agreement with experiments. The main drawback of this approach is that a small electronic repulsion is enough to make bipolaron formation energetically highly unfavorable, and in cuprates local Coulomb repulsion can by no means be neglected. Another theoretical prediction available is based on the idea of a quantum critical point at optimal doping: By analyzing the effects of critical fluctuations, Andergassen et al. proposed a consistent picture of the experimental observation. 6 Yet, to the best of our knowledge, no calculation has been done so far to see whether or not an isotope effect on T * is to be expected within probably the simplest model for cuprates, namely, a one-band tight-binding model for electrons or holes on the copper sites with nearest-neighbor and diagonal hopping t and t , respectively, experiencing a local Hubbard repulsion...