The intermediates formed upon the interaction of methane with Cu-modified ZSM-5 zeolites (Cu/H-ZSM-5) have been analyzed with solid-state NMR spectroscopy and DFT methods. Methane activation by Cu/H-ZSM-5 zeolites gives rise to three distinct surface methoxy-like species (-O-CH3) detected by 13C MAS NMR spectroscopy with specific chemical shifts in the range of 53-63 ppm. DFT calculations on representative cluster models of different sites potentially present in Cu/H-ZSM-5 have been used to assign these signals to (i) methanol adsorbed on two neighboring Cu sites (Cu-(HOCH3)-Cu, 62.6 ppm), (ii) methanol adsorbed on zeolite Brønsted acid sites (52.9 ppm), and (iii) lattice-bound methoxy groups (Si-O(CH3)-Al, 58.6). The formation of these methoxy-like intermediates depends on the Cu loading and, accordingly, the type of Cu species in the Cu/H-ZSM-5 zeolite. For the sample with low (0.1 wt %) Cu loading containing exclusively mononuclear isolated Cu species, only the intermediates ii and iii have been detected. The Cu-bound intermediate (i) is formed upon methane activation by multinuclear Cu sites featuring Cu-O-Cu bridging moieties present in the materials with relatively higher Cu loading (1.38 wt %). The presented results indicate that methane activation by Cu/H-ZSM-5 can be promoted by both mono- and multinuclear Cu species confined in the zeolite matrix.