TNF-related weak inducer of apoptosis (TWEAK) and TNF-related apoptosis-inducing ligand (TRAIL) are members of TNF superfamily, which has various roles in immunologic and inflammatory reactions in the organism. Pathophysiology in bipolar disorder is still under investigation and altered serum levels of cytokines are often encountered. Aim of this study is to detect serum TWEAK and TRAIL levels of patients with bipolar disorder and healthy controls. For this purpose, 55 patients with bipolar disorder -27 manic episode (ME), 28 remission (RE) and 29 healthy controls (HC) were included. TWEAK levels of ME and RE groups were significantly lower than HC. TWEAK levels of bipolar patients (BP) were also lower than HC. TRAIL levels of ME, RE, HC groups and BP, HC groups were statistically similar. In our knowledge, this is the first study concerning about TWEAK and TRAIL levels in bipolar disorder and our results pointed that TWEAK-related immune response might be impaired in bipolar disorder, but our study fails to eradicate the confounders such as medication, smoking and body mass index. Studies having larger samples and limited confounders are needed to be able to evaluate these changes better and detect possible alterations about TRAIL and other TNF superfamily members.