The objective of this study is to investigate and compare serum levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Behçet's disease. Patients with a diagnosis of RA (n = 20), SLE (n = 20) and Behçet's disease (n = 20) and a healthy control group (n = 19) were included in our study. Disease activity indexes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were recorded in the patient groups. Serum TWEAK levels were measured with available commercial enzyme linked immunosorbent assay kits. The serum TWEAK levels were significantly higher in all patient groups compared to the control group. However, no significant difference was found in paired comparisons among patient groups. When the patients with high disease activity scores were compared to patients with low disease activity scores in RA, SLE and Behçet’s disease subgroups, there was no significant difference in terms of TWEAK levels. Hypertension, atherosclerosis, diabetes mellitus and smoking had no effect on serum TWEAK levels. In correlation analysis, although serum TWEAK levels showed a significant negative correlation with age (r = -0.361, p = 0.005), there was no significant correlation with body mass index (BMI), ESR, and CRP levels. In RA, SLE and Behçet's disease, although different inflammatory pathways and different cytokine release patterns play a role in their pathogenesis, the similar increase in serum TWEAK levels and the absence of a relationship with the disease activity scores reflecting the last stage of inflammation may indicate that the TWEAK / Fn14 pathway plays a role in earlier stages where the inflammatory pathways have not differentiated yet.