To test an attribution–emotion model of reactions to chronic fatigue syndrome/myalgic encephalomyelitis, 30 significant others of 30 adult patients with chronic fatigue syndrome/myalgic encephalomyelitis were administered a semi-structured interview about their beliefs regarding the patient’s illness and completed questionnaire measures of distress and behavioural responses to the patient. Spontaneous causal explanations (attributions) for illness events, symptom exacerbation and negative patient mood were extracted and coded. Significant others’ distress and negative behavioural responses towards the chronic fatigue syndrome/myalgic encephalomyelitis patient were associated with attributing illness events to causes personal and internal to the patient. Our findings may inform the future family-based interventions for chronic fatigue syndrome/myalgic encephalomyelitis.