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Background: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS)., Aim: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS., Methods: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS)., Results: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls ( F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups ( P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group ( F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score ( r = -0.389, P = 0.032) and avolition/asociality subscore ( r = -0.387, P = 0.026)., Conclusion: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients., Competing Interests: Conflict-of-interest statement: No conflict of interest was disclosed for each author., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)