Objective and Background: To evaluate whether increased levels of high-sensitivity C- reactive protein (hs-CRP) observed in individuals with bipolar disorder (BD) compared to healthy controls (HCs) could be influenced by a previous exposure to early life stress (ELS) independently from other explanatory or background variables, including age, body mass index (BMI), and the presence of cooccurring mental disorders.Method: In this case-control study, we included 142 healthy controls and 92 bipolar I and II patients. The Childhood Trauma Questionnaire was administered in a subset of 30 female patients with BD and 31 female HCs, and plasma hs-CRP was measured in all subjects. Multivariable models adjusted the data for the possible confounding variables. Results: Serum hs-CRP levels were significantly higher in patients with BD compared to HCs. However, after controlling for BMI, these differences were no longer significant. Around 55% of the variance in hs-CRP was explained by cumulative and independent effects of age, BMI and childhood trauma, especially sexual abuse. Conclusion: Our results show that increased hs-CRP levels in BD patients are more related to childhood trauma, especially sexual abuse, age and BMI than to a diagnosis of BD per se. These data suggest that peripheral inflammation may underpin the well-known detrimental effects of childhood maltreatment and obesity in the course of BD. Hs-CRP data are difficult to interpret if they are not adjusted for effects of BMI and age.