Objective: ADHD, a prevalent neurodevelopmental disorder affecting 5−7% of children and adolescents, is characterized by inattention, hyperactivity, and impulsivity, impacting social and academic functioning. Its complex etiology includes genetic, environmental, and inflammatory factors. In the present research, we aimed to compare serum CRP, TNF-α, IL-6, IFN-γ, TWEAK, neopterin and zinc levels in drug-naive ADHD patients and healthy controls. Methods: This study included 50 drug-naïve ADHD patients (aged 8−18) and 37 healthy controls. Psychiatric diagnoses were based on DSM-5 criteria. Blood samples were analyzed for inflammatory markers, including CRP, TNF-α, IL-6, IFN-γ, TWEAK, neopterin, and zinc. Statistical analyses were performed using SPSS. Results: The study found no significant differences in age, sex, or BMI between individuals with ADHD and the control group. Regarding inflammatory markers, ADHD patients demonstrated significantly lower levels of TWEAK and higher levels of CRP compared to controls. However, no differences were observed in the levels of TNF-α, IL-6, IFN-γ, zinc, or neopterin. When examining ADHD subtypes, it was noted that individuals with the inattentive subtype had markedly lower TWEAK levels and higher CRP levels than the control group. Conclusion This finding particularly supports that TWEAK levels could be a significant marker both for ADHD and the predominantly inattentive subtype. Additionally, a correlation was identified between IFN-γ levels and psychosomatic symptoms, and this positive correlation suggests that this cytokine may be associated with specific ADHD symptoms. This study highlights the role of neuroinflammatory processes in ADHD and the etiological distinction of the predominantly inattentive ADHD subtype from other subtypes in the literature. Future research should validate these findings through larger and longitudinal studies.