The impact of drying on the ultrastructure of fresh wood was studied by deuterium exchange Coupled with FT-IR analysis. This fundamental investigation demonstrated that water removal leads to irreversible alterations of the wood structure, namely, supramolecular rearrangements between wood polymers. The deuteration of fresh wood was shown to be fully reversible by it subsequent exposure of the deuterated sample to water (reprotonation) Therefore, the presence of any OD groups in deuterated and then dried wood samples after reprotonation is a clear indicator of reduced accessibility. The extent of changes was affected by drying temperature and relative humidity Application of this methodology for the evaluation of chemical pulp sample (reference material) resulted in similar response, only more pronounced Two hypothetical alternatives were proposed for accessibility reduction in dried wood (i) irreversible aggregation of cellulose microfibrils and (it) irreversible stiffening of the hemicellulose/lignin matrix that extensively swells when exposed to water