Accumulating data presented that tryptophan metabolic pathway (TMP) may play a role in attention-deficit/hyperactivity disorder (ADHD). However, no study have investigated potential role of TMP in disruptive behavior disorders coexisting with ADHD. This study compared serum levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine and 3-hydroxyantranilic acid in medication-free children with ADHD combined presentation (ADHD-C), with ADHD-C and oppositional defiant disorder (ODD), and with ADHD-C and conduct disorder (CD) versus healthy controls. The study also compared several ratios that are previously suggested to reflect the activities of the KP enzymes (kynurenine/tryptophan, kynurenic acid/kynurenine, 3-hydroxykynurenine/kynurenine) or neuroprotective activity (kynurenic acid/3-hydroxykynurenine) among groups. A total of 122 patients were enrolled: 46 children with ADHD-C alone, 43 children with ADHD-C+ODD, 33 children with ADHD-C+CD and 50 healthy controls. Targeted biochemical molecules were assessed by liquid chromatography-mass spectrometry/mass spectrometry. Compared to control group, serum kynurenine levels were significantly higher in the ADHD-C group, serum 3-hydroxykynurenine levels were significantly lower in the ADHD-C and ADHD-C+ODD groups, the serum kynurenic acid/kynurenine ratio was significantly higher in the ADHD-C, ADHD-C+ODD and ADHD-C+CD groups, and the serum 3-hydroxykynurenine/kynurenine ratio was significantly lower in the ADHD-C group. These findings suggest that TMP may play a role in the pathophysiology of ADHD-C.