Objectives Chronic Fatigue Syndrome (CFS) is a debilitating condition that affects 0.2–0.4% of the population. First‐line treatments are Cognitive Behaviour Therapy or graded exercise therapy; however, these treatments yield only moderate effect sizes. Emerging research suggests that anxiety about health may be common in CFS. Health anxiety treatment models demonstrate good therapeutic outcomes; however, these models have yet to be applied to CFS. This paper describes the application of a novel cognitive behavioural approach to the treatment of both physical and anxiety related symptoms in a patient with CFS and, furthermore, presents a conceptual hypothesis regarding the mutually maintaining relationship between these two co‐occurring conditions. Design A single‐case design was used, with pre‐data, post‐data and follow‐up data. The cognitive behavioural model of health anxiety was adapted and delivered as an eight‐session intervention. The intervention was driven by an individualized formulation developed collaboratively with the patient. Results The application of this approach generated reliable and clinically significant reductions in physical and psychological symptoms, which were maintained at 12‐month follow‐up. The participant no longer fulfilled the criteria for CFS or health anxiety following eight treatment sessions. The treatment approach was found to be agreeable to the patient. All treatment hypotheses were supported. Conclusions An adapted cognitive behavioural approach to treating CFS and health anxiety yields positive results and shows promise for application to the broader CFS population. Copyright © 2016 John Wiley & Sons, Ltd. Key Practitioner Messages Chronic Fatigue Syndrome (CFS) is a debilitating condition that is difficult to treat successfully; first‐line recommended treatments achieve only moderate effect sizes. Anxiety, particularly about health, is reported to be common in CFS. However, anxiety is not specifically targeted within treatment and may negatively influence outcome due to the potentially mutually maintaining nature of these complex conditions. The present study demonstrates that an integrated treatment approach designed to encompass physical and psychological symptoms yields reliable and clinically significant outcomes in 50% of time recommend for first line treatments. Results reflected non‐case level status for both CFS and health anxiety at end of treatment, in addition to reductions across all clinical measures. This study demonstrates the fundamental importance of an individualized, rather than generic, treatment approach to complex cases; the ‘meaning’ of experience is a central tenet within a cognitive approach that should be reflected in treatment.