INTRODUCTION: Chronic fatigue syndrome, termed myalgic encephalomyelitis in the United Kingdom (CFS/ME), is a debilitating condition involving severe exhaustion, cognitive difficulties, educational and vocational losses, and disruption of social activities and relationships. CFS/ME may affect volition (that is, value, interest and sense of competence). PURPOSE: To test Model of Human Occupation (MOHO) concepts by comparing young people with and without CFS/ME in terms of occupational participation, volition and health-related quality of life during infection and over time. METHOD: Three hundred and one people (12-18 years old) diagnosed with glandular fever were evaluated at the time of acute infection (baseline). Six months following diagnosis, 39 of them met the criteria for CFS/ME. A further 39 who recovered were randomly selected and matched to CFS/ME participants. Both groups were re-evaluated at 12 months and 24 months. The Occupational Self Assessment and the Child General Health Questionnaire were used to compare occupational participation. RESULTS: Those with CFS/ME reported lower levels of perceived competency, more difficulties with physical functioning and poorer general health status than those who recovered. CONCLUSION: Those with CFS/ME report lower perceived competency, and compromises in physical functioning, school performance, social activities, emotional functioning and general health. This supports the MOHO assertion that impairments affect volition and quality of life.