CuO is the prototype compound of cuprate superconductors, so understanding its electronic structures will facilitate the study of the pairing mechanism and miscellaneous states of high-temperature superconductors. We prepared uniform CuO nanocrystals (7–100 nm) and studied their size-dependent Raman scattering spectra. The relative variation between the two-phonon scattering band (2B_g) and the one-phonon band (B_g) indicates a decreasing electron–phonon coupling with reducing size, which unveils the dominant Fröhlich electron–phonon coupling, as indicated by Devreese, but not the small polaron in CuO. Moreover, the anomalous enhancement of the multi-phonon band at a critical size and 1D structure at room temperature is attributable to an enhanced electron–phonon coupling accompanied by phonon–plasmon coupling, i.e., the ‘plasphon’ proposed by Alexandrov et al in 1981.