Background <p>Overwhelming evidence suggests that adults with chronic pain have altered brain structure and related networks. However, little is currently known regarding changes in structural gray matter and structural covariance networks (SCNs) in children with multisite pain (MP) and their potential relationships with biopsychosocial characteristics.</p> Methods <p>This study enrolled 444 children with MP and 444 matched controls from the Adolescent Brain Cognitive Development Study. All participants underwent magnetic resonance imaging (MRI) scans following biopsychosocial assessment. Then, SCNs matrices were constructed by the Brain Connectivity Toolbox based on both cortical thickness (CT) and cortical surface area (CSA) among 415 children with MP and 404 controls. Nonparametric permutation tests were employed to examine the group differences in these matrices.</p> Results <p>Compared with controls, children with MP exhibited both lower CSA and CT in widespread regions involved in the pain matrix, including the anterior cingulate cortex (ACC), middle frontal gyrus (MFG), superior frontal gyrus (SFG), and anterior insula (aIns). While there were no significant group differences in global network measures, children with MP exhibited alterations in nodal network measures in brain regions including the ACC, MFG, and aIns. Besides, children with MP showed significant relationships between abnormal structural gray matter and biopsychosocial characteristics, including general somatic symptoms, conduct disorder symptoms, and sleep quality.</p> Conclusions <p>Children with MP exhibited abnormal structural gray matter and SCNs in brain regions involved in the pain matrix, which were further associated with biopsychosocial characteristics. These findings could suggest individualized treatments for children with MP, such as transcranial magnetic stimulation therapy, that focus on specific brain nodes within the pain matrix and improve related biopsychosocial characteristics.</p> Graphical Abstract <p></p>