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Background Divorce and living alone are associated with several adverse health outcomes. There is however very limited knowledge on the potential effects of exposure across the life course. The aim of this study is to investigate whether accumulated number of divorces/partnership breakups or years lived alone across 26 years of adult life, is associated with levels of low grade inflammation and if vulnerability with regards to gender or educational level can be identified. Methods 4,835 participants from Copenhagen Aging and Midlife Biobank (CAMB) aged 48-62 were included. Accumulated number of partnership breakups and years living alone, were retrieved from a national standardized annual register. Inflammatory markers, Interleukin-6 (IL-6) and high sensitivity C-Reactive Protein (hsCRP), were measured in plasma samples. Multivariate linear regression analyses were adjusted for age, educational level, early major life events, BMI, chronic diseases, medicinal intake that affects inflammation, acute inflammation, and personality scores (neuroticism, agreeableness, conscientiousness). Results For men, two or more partnership breakups as well as living alone for 7+ years was associated with significantly higher levels of and inflammatory markers, i.e. 12-17% higher level of hsCRP and IL6 compared to the reference groups (no break-ups/0-1 years living alone) p-values Conclusions The findings suggest a strong association between accumulated number of partnership breakups or years lived alone across 26 year of adult life and low grade inflammation for middle-aged men but not for women. No specific vulnerability among the lower was identified. The findings points towards the importance of developing tailored preventive initiatives to males experiencing several partner-break-ups or who lives alone for many years. Key messages Two or more partnership breakups or 7+ years lived alone across 26 year of adult life is associated with increased low grade inflammation for middle-aged men but not for women. No increased vulnerability among the low educated was identified.