Objective: To investigate differences between young children, adolescents and adults with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Study design: Comparison of clinical cohorts from 8 paediatric and 27 adult CFS/ME services in the UK and a paediatric randomised controlled trial from the Netherlands. Outcome measures include: fatigue (UK - Chalder Fatigue Scale); Disability (UK – SF-36 physical function subscale; Netherlands – CHQ-CF87); school attendance, pain, anxiety and depression (UK - Hospital Anxiety & Depression Scale, Spence Children’s Anxiety Scale; Netherlands – Spielberger State-Trait Anxiety Inventory for Children, Children’s Depression Inventory); symptoms; time-to-assessment; and BMI. We used multinomial regression to compare younger (age <12 years) and older (age 12-18 years) children with adults, and logistic regression to compare UK and Dutch adolescents. Results: Younger children had a more equal gender balance compared to adolescents and adults. Adults had more disability and fatigue and had been ill for longer. Younger children were less likely to have cognitive symptoms (odds ratio (OR) 0.18 (95% CI 0.13, 0.25)) and more likely to present with a sore throat (OR 1.42 (1.07, 1.90). Adolescents were more likely to have headaches (81.1%, OR 1.56 (1.36, 1.80)) and less likely to have tender lymph nodes, palpitations, dizziness, general malaise and pain, compared to adults. Adolescents were more likely to have co-morbid depression (OR 1.51 (1.33, 1.72)) and less likely to have anxiety (OR 0.46 (0.41, 0.53)) compared to adults. Conclusions: Paediatricians need to recognise that children with CFS/ME present differently from adults. Whether these differences reflect underlying aetiopathology requires further investigation.