Objectives: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (μg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. Methods: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). Results: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. Conclusions: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.