Background: Chronic fatigue syndrome (CFS) is a chronic disease characterized by various symptoms such as pathological fatigue, cognitive dysfunction, and inability to recover energy after waking up. The Yijinjing, a kind of health care practice from ancient China, consists of 12 movements, and it is considered as one of the complementary and alternative medicine (CAM) for health maintenance, health care, and disease healing. In this study, multiple scales were used to evaluate the effects of Yijinjing intervention on the clinical symptoms of CFS. Patients and Methods: Forty patients with CFS were randomly assigned to Yijinjing group and the cognitive behavior therapy (CBT) group separately. The Yijinjing intervention was practiced 6 times per week, among which one exercise should be guided by the teacher of the faculty in the university, and another 5 times should be finished at home over 12 consecutive weeks. Similarly, the control group received cognitive education, including popular science lectures and psychological counseling related to CFS prevention and treatment for 12 weeks. Multidimensional Fatigue Inventory-20 (MFI-20), Short Form 36-item Health Survey (SF-36), and Pittsburgh Sleep Quality Index (PSQI) were assessed before and after intervention. Results: Intra-group analysis showed that the differences in MFI-20, SF-36, and PSQI were statistically significant (p < 0.05) after the intervention of 12 weeks Yijinjing intervention. Compared with the CBT group, the differences in MFI-20 and PSQI of the Yijinjing group were statistically significant (p < 0.05), but SF-36 was superior to the CBT group in terms of physical function, bodily pain, general health, and vitality (p < 0.05). Conclusion: Yijinjing can significantly improve sleep disorders, fatigue, and quality of life in patients with CFS and is superior to behavioral cognitive education in pain and vitality. The study was registered with Chinese Clinical Trial Registry: ChiCTR-INR-17010694.

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