AbstractCross-laminated timber (CLT) panels have been adopted as main structural elements in the mass timber constructions that have recently caught the attention from different stakeholders. The enhanced mechanical performances allow the design of impressive structures like tall buildings. However, not so much is known about the performance of CLT panels under service life condition. In this context, the strain distribution taken from an experimental campaign carried out using Digital Image Correlation (DIC) is considered as a basis to investigate the stress distribution presented by CLT panels under cyclic moisture variations. Four CLT configurations promoting different moisture flow were conditioned in climatic chambers for 324 days at a constant temperature of 20°C, and with a humidity cycle varying every 21 days between 30% and 90%, getting constant at 65% after the first 142 days. Strains calculated through DIC, along with moduli of elasticity defined by ultrasound tests, were used to estimate strained and released stresses, respectively, before and after cutting specimens. Results show that sealing CLT panels play an insignificant role on distribution of stress induced by cyclic moisture, but peak stresses, both tension and compression resulted from wetting and drying cycles, respectively, were reduced in many specimens, especially when longitudinal faces were sealed. Moreover, as general recommendations to take in the design of CLT panels regarding moisture changes, it is possible to identify the need to limit the longitudinal length of panels, to use more thin layers rather than less thick ones, and to protect panels in the longitudinal direction, owing to high stress concentrated along this direction, particularly in the borders.