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Introduction Current evidence suggests that pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-α) may play an important role in the pathophysiology of bipolar disorder (BD). Our study aims to compare BD patients and controls in terms of serum TNF-α, soluble tumor necrosis factor receptor 1 and soluble tumor necrosis factor receptor 2 (sTNF-R1, sTNF-R2) levels in different phases of BD. Methods Eighty-three patients with BD type 1 (27 manic, 22 depressive and 34 euthymic) and twenty-nine healthy controls were included in the study. Serum levels of TNF-α, sTNF-R1, sTNF-R2 levels were evaluated with ELISA kit. Results Levels of sTNF-R1 were showed a statistically significant difference between groups. Levels of sTNF-R1 were higher in depression or mania patients than euthymia patients and control subjects. A statistically significant difference in the serum level of sTNF-R1 between patients in acute episode (mania and depression) group and stabile (patients in euthymic episode and controls) group was found in logistic regression analysis. The probability of having acute episode increased threefold for each unit increase in serum level of sTNF-R1. There was no statistically significant difference between the mean serum values of TNF-α and sTNF-R2 between the groups. Conclusions sTNF-R1 production was different between acute episode patients and controls or stable BD patients. The result of this study confirms that TNF-R1 may be a state marker representing disease activity for BD.