Aim: To assess sex-related differences in the pathohistological features of the human lacrimal gland and to investigate age-related and sex-related differences in stereologically measured volume density of the secretory tissue, connective tissue, and fat. Methods: We performed an observational analysis of acinar atrophy, periacinar fibrosis, periductal fibrosis, ductal dilation, ductal proliferation, fatty infiltration, and lymphocyte infiltration of hematoxylin and eosin-stained lacrimal gland samples from 81 cornea donors. Stereological analysis of the volume density of the secretory tissue, connective tissue, and fat was performed on samples from 66 donors. Results: Up to 69% of all samples showed degenerative changes. Female samples had a higher frequency of all observed degenerative changes, except ductal dilation. While acinar atrophy was significantly more prevalent in women, ductal dilation was significantly more prevalent in men. Stereological analysis indicated lower portions of acini and higher portions of connective tissue and fat, as well as a more pronounced age-related progression of degenerative changes in female samples. Conclusion: Female lacrimal glands are more susceptible to degeneration, and this susceptibility could play an important role in the higher incidence of dry eye disease in older women. A further stereological analysis using more samples from younger age groups is needed to elucidate age-related and sex-related differences in the structure of the human lacrimal gland and their impact on dry eye disease.