We found the serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor‐α, was significantly higher in treatment‐resistant than in remitted major depressive disorder patients, suggesting that serum soluble interleukin 6 receptor could be a useful biomarker for treatment‐resistant major depressive disorder. Here, IL6R is linked to major depressive disorder.