Introduction: There has been no study in the literature evaluating serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) levels in attention-deficit/hyperactivity disorder (ADHD). Therefore, we performed the present study to specifically measure serum TWEAK levels to see whether or not its eventual alterations might have an etiopathogenetic significance in children with ADHD. Subjects and methods: A total of 49 treatment-naive children with ADHD and 39 healthy controls were included in the present study. The severities of ADHD and conduct disorder symptoms were assessed via parent- and teacher-rated questionnaires. Venous blood samples were collected, and serum TWEAK levels were measured. Results: Serum TWEAK levels of the ADHD group were significantly lower than the control group. Conclusions: This study shows that ADHD patients have decreased serum TWEAK levels, suggesting a possible involvement of TWEAK in the etiopathogenesis of ADHD.