The formation of hydroxo complexes based on a calix[6]trisimidazole ligand is described. Deprotonation of the mononuclear Cu(II)-aqua complex gives rise to a dinuclear bis(mu-hydroxo) complex that has been characterized by X-ray diffraction analysis. Spectroscopic studies (EPR and UV-vis), conducted in dichloromethane solutions in the presence of various coordinating cosolvents (DMF, EtOH, or RCN) or with acetamide, revealed the coexistence of a mononuclear hydroxo species. The latter could be trapped by acetic acid to provide an acetato-Cu(II) complex that presents close spectroscopic features. An EXAFS study first conducted on the hydroxo-Cu(II) complex led to an excellent fit for the dinuclear core. It then allowed for the characterization of the mononuclear acetato complex with an acetamide guest included in the calixarene cavity. Hence, this study illustrates the flexibility of calixarenebased ligands and the role of the second coordination sphere in the stabilization of acidic or basic Cu(II) complexes.