BackgroundPsychological stress, as an important cofactor in the development of many acute and chronic diseases, is crucial for general health or well-being, and improved markers are needed to distinguish situations of progressive pathological development, such as depression, anxiety, or burnout, to be recognized at an early stage. Epigenetic biomarkers play an important role in the early detection and treatment of complex diseases such as cancer, and metabolic or mental disorders. Therefore, this study aimed to identify so-called miRNAs, which would be suitable as stress-related biomarkers.Methods and ResultsIn this study, 173 participants (36.4% males, and 63.6% females) were interviewed about stress, stress-related diseases, lifestyle, and diet to assess their acute and chronic psychological stress status. Using qPCR analysis, 13 different miRNAs (miR-10a-5p, miR-15a-5p, miR-16-5p, miR-19b-3p, miR-26b-5p, miR-29c-3p, miR-106b-5p, miR-126-3p, miR-142-3p, let-7a-5p, let-7g-5p, miR-21-5p, and miR-877-5p) were analyzed in dried capillary blood samples. Four miRNAs were identified, miR-10a-5p, miR-15a-5p, let-7a-5p, and let-7g-5p (p< 0.05), which could be used as possible candidates for measuring pathological forms of acute or chronic stress. Let-7a-5p, let-7g-5p, and miR-15a-5p (p< 0.05) were also significantly higher in subjects with at least one stress-related disease. Further, correlations were identified between let-7a-5p and meat consumption (p< 0.05) and between miR-15a-5p and coffee consumption (p< 0.05).ConclusionThe examination of these four miRNAs as biomarkers using a minimally invasive method offers the possibility of detecting health problems at an early stage and counteracting them to maintain general and mental health.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11033-023-08467-5.