Cell wall measures allow for direct assessment of wood modification without the adverse effect of varying density and microstructure. In this study, cell wall properties of recent and archeological oak wood from the Vasa shipwreck were investigated for cell wall stiffness, hardness and creep with respect to effects of chemical degradation, impregnation with a preservation agent, namely polyethylene glycol, and moisture. For this purpose, nanoindentation tests were performed at varying relative humidity, leading to different moisture contents in the wood samples. Concurrently, microstructural and chemical characterization of the material was conducted. Impregnated and untreated recent oak wood showed a softening effect of both moisture and preservation agent at the wood cell wall level. On the contrary, increased stiffness was found for non-impregnated Vasa oak, which can be explained by aging-related modifications in cell wall components. These effects were counteracted by the softening effect of polyethylene glycol in the impregnated Vasa material, where a lower overall stiffness was measured. The reverse effect of the preservation agent and moisture, namely increased indentation creep of the cell wall material, was revealed. The loss of acetyl groups in the hemicelluloses explained the decreased hygroscopicity of the Vasa oak. In the impregnated Vasa oak, this effect seemed to be partly counteracted by the presence of low-molecular polyethylene glycol contributing to higher hygroscopicity of the cell wall. Thus, the higher overall sorptive capacity of the impregnated Vasa material, with respect to the non-impregnated material, was detected, which has resulted in a sorptive behavior similar to that of recent oak wood. The proposed approach requires only small amounts of material, making it especially suitable for application to precious historical wooden artifacts.