Objectives: At least 30% of young people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) also have symptoms of depression. This systematic review aimed to establish which treatment approaches for depression are effective and whether comorbid depression mediates outcomeSetting: A systematic review was udnertaken. the search terms were entered into MEDLINE EMBASE, PsycInfo and the Cochrane library.Participants Inclusion and exclusion criteria were applied to identify relevant papers. Inclusion criteria were children age <18, with CFS/ME, defined using CDC, NICE or Oxford criteria, and having completed a valid assessment for depression.Results 9 studies were identified which met the inclusion criteria, but none specifically tested treatments for paediatric CFS/ME with depression and none stratified outcome for those who were depressed compared with those who were not depressed. There is no consistent treatment approach for children with CFS/ME and comorbid depression, although cognitive–behavioural therapy for CFS/ME and a multicomponent inpatient programme for CFS/ME have shown some promise in reducing depressive symptoms. An antiviral medication in a small scale, retrospective, uncontrolled study suggested possible benefit.Conclusions It is not possible to determine what treatment approaches are effective for depression in paediatric CFS/ME, nor to determine the impact of depression on the outcome of CFS/ME treatment. Young people with significant depression tend to have been excluded from previous treatment studies.