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Summary: Background: During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather‐exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF). Objectives: To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults. Methods: Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18–40 years and 40 aged ≥ 70 years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface texture was done (Dermal Texture Index, DTI). Potential confounders were registered and adjusted for. Results: In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self‐reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the summer, and female participants had higher NMF levels than male participants. Conclusions: Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis. [ABSTRACT FROM AUTHOR]