Objective Chronic fatigue syndrome (CFS) describes a condition that is primarily characterized by fatigue and flu-like symptoms that are not alleviated by rest. This study investigated the relationship among metacognitions, negative emotions, and symptom severity in CFS. Methods A total of 96 patients who had received a diagnosis of CFS according to the Oxford Criteria completed a battery of self-report measures that consisted of the Depression Anxiety Stress Scales, the 30-Item Metacognitions Questionnaire, the Chalder Fatigue Questionnaire (CFQ), and the RAND 36-Item Short-Form Health Survey-Physical Functioning. Results Correlation analyses showed that negative emotions and metacognitions were positively correlated with measures of symptom severity and that metacognitions were a better predictor of symptom severity than anxiety and depression. Hierarchical regression analyses indicated that (1) lack of cognitive confidence predicted both mental and physical factors of the CFQ and physical functioning independently of negative emotions and (2) beliefs about the need to control thoughts predicted the mental factor of the CFQ independently of negative emotions and lack of cognitive confidence. Conclusion The data support the potential application of the metacognitive model of psychological disorder to understanding CFS.