We report on dynamic properties of carbon monoxy myoglobin (MbCO) embedded in trehalose matrices of different water content, studied by FTIR spectroscopy and CO rebinding after flash-photolysis. FTIR spectroscopy was used to study the thermal behavior of the bound CO stretching and of the adjacent bands arising from trehalose and residual water, as a function of the sample water content. These measurements enabled us to get information on the relation between the interconversion among A substates (as evidenced by the thermal behavior of the CO stretching band) and the dynamics of the trehalose-water matrix. Under condition of drought, the protein internal dynamics is tightly coupled to the dynamics of the external matrix and is modulated by traces of residual water. Under such condition, substates interconversion is hindered due to extreme increase of energy barriers. At variance sizeable substates interconversion takes place following a small water uptake, obtained by exposure of the dry sample to a nondry surrounding atmosphere. FTIR results were in full agreement with flash-photolysis data. In particular, the heme pocket dynamics, which regulates the migration of the flashed off CO molecule within the protein matrix, can be well described on the basis of the information obtained by FTIR measurements. Under condition of drought, in which vanishing temperature dependence of the CO stretching band is observed, the rebinding kinetics is governed by quasi-static rate constant distributions. At variance, stretched exponentials describe geminate rebinding following slight water uptake by the sample, which, as shown by FTIR, brings about interconversion among conformational A substates.