The microporous metal-organic framework Ni2(dhtp) (H 4dhtp ) 2,5-dihydroxyterephtalic acid) is a 3D network that maintains crystallinity and porosity after solvent removal. A mild thermal treatment in high vacuo at 393 K removes completely water allowing to obtain a MOF material with honeycomb structure able to strongly coordinate CO at room temperature. In this contribution, the reactivity toward CO of CPO-27-Ni has been studied by the combined use of infrared, extended X-ray absorption fine structure, X-ray absorption near edge structure, and UV-vis spectropies and microcalorimetry. Most of the Ni2+ sites are involved in the interaction (about 80%), forming 1:1 linear adducts whose interaction enthalpy is slightly above 50 kJ/mol. In the presence of CO, a large modification of the vibrational and electronic properties of the material with respect to the dehydrated one has been observed.