ObjectivePsychological Flexibility (PF) is a relatively new concept in physical health. It can be defined as an overarching process of being able to accept the presence of wanted/unwanted experiences, choosing whether to change or persist in behaviour in response to those experiences. Associations between processes of PF and quality of life (QoL) have been found in long-term health conditions such as chronic pain, PF has not yet been applied to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). MethodsChanges in PF, fatigue severity and QoL were examined in one hundred and sixty-five patients with CFS/ME engaged in a six-week outpatient interdisciplinary group treatment programme. Participants were assessed using a series of self-report measures at the start of the start (T1) and end of a six-week programme (T2) and at six months follow up (T3). ResultsSignificant changes in PF and QoL were observed from pre-treatment (T1) to post treatment follow-up (T2 and T3); changes in fatigue severity were observed from T1 to T3 only. Controlling for fatigue severity, changes in the PF dimension of activity/occupational engagement were associated with improvement in QoL at six month follow up (T3) but not at six weeks post programme (T2). ConclusionFindings indicate an interdisciplinary group treatment approach for people with CFS/ME may be associated with improved QoL, processes of PF and fatigue severity, supporting a link between PF and long term health conditions. Results highlight links between PF and patient QoL in CFS/ME and the value of interdisciplinary treatment approaches in this patient population.