Natural cellulose readily interacts with water due to the abundance of hydroxyl groups in its molecular structure. These interactions play a crucial role in cellulose processing and significantly affect its properties and performance across various environmental conditions. In particular, natural cellulosic materials exhibit high sensitivity to moisture fluctuations, which can alter their structural integrity and mechanical behavior. Understanding humidity-induced changes in cellulose is therefore essential for engineering robust materials for applications in energy, (opto)electronics, sensing, decontamination, and filtration systems.Man-made cellulose materials obtained via the transition of native cellulose I into cellulose II via dissolution and regeneration introduce increased possibilities of controlling some of the material’s physical properties. In this study, the crystallographic fingerprint of cellulose II determined from X-ray diffraction measurements (XRD) was changed between the samples by introducing alcohols of different chain lengths in the regeneration process. The moisture response of the different cellulose II samples was studied in an environmental scanning probe microscopy, simultaneously controlling the humidity.  The microscopic structural changes induced by moisture and the corresponding nanomechanical properties of the regenerated cellulose samples were captured. The study provides critical insights into the moisture-dependent behavior of cellulose, supporting the development of advanced regenerated cellulose-based materials with enhanced stability and performance.