Objectives <p>Chronic non-bacterial osteomyelitis (CNO) is the most common autoinflammatory bone disease in children and adolescents. This study investigated the progression of CNO lesions during therapy and the potential impact of sarcopenia on disease progression, utilizing routine MRI.</p> Methods <p>A retrospective analysis of MRI examinations was conducted on 29 children and adolescents with CNO. CNO lesions were segmented. Sarcopenia was assessed using the total psoas muscle index (PMI) at lumbar vertebral levels L3/4 and L4/5. Measurements were taken at four time points during the disease course (T1: baseline, T2–T4: follow-up). Based on the PMI, patients were classified as sarcopenic or non-sarcopenic, and the progression of CNO lesions and the impact of sarcopenia were analyzed.</p> Results <p>A total of 29 patients, aged 1–16 years, were included in the study, with 13 males and 16 females. Patients with sarcopenia had a significantly larger mean lesion area (868.95 mm², SD = 684.49) compared to those without sarcopenia (636.11 mm², SD = 832.41); <i>p</i> = 0.042, <i>d</i> = 0.4). The comparison between the two patient groups revealed a consistently lower percentage reduction in lesion size for the sarcopenic patients at all time points. Notably, the difference between T1 and T3 was statistically significant (<i>p</i> = 0.045, <i>d</i> = 0.82).</p> Conclusion <p>The present study indicates that sarcopenia may serve as a negative prognostic factor in the treatment of CNO. Incorporating sarcopenia assessment as an additional parameter in routine whole-body MRI examinations could enhance the evaluation process.</p> Critical relevance statement <p>Sarcopenia can be assessed using routine whole-body MRI in patients with CNO and may serve as a negative prognostic factor, potentially enhancing the evaluation process.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Whole-body MRI is crucial for diagnosing and monitoring CNO.</p> </ItemContent> <ItemContent> <p>Routine whole-body MRI in CNO patients can also be used to assess sarcopenia as an additional parameter.</p> </ItemContent> <ItemContent> <p>Sarcopenia may act as a negative prognostic factor in CNO treatment, potentially improving the evaluation process.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>