Abstract：Objective：To observe the clinical effect of micro acupotomy combined with Multivitamin and Minerals Tablets for chronic fatigue syndrome. Methods：A total of 90 cases of patients with chronic fatigue syndrome were divided into the control group and the treatment group according to the random number table method，with 45 cases in each group. The control group was treated with Multivitamin and Minerals Tablets (29)， and the treatment group was additionally treated with micro acupotomy based on the treatment of the control group. The scores of Fatigue Severity Scale (FSS)， Short- form of McGill Pain Questionnaire (SF-MPQ)，and traditional Chinese medicine (TCM) syndrome were compared between the two groups before and after treatment. Clinical effects and the incidence of adverse reactions were evaluated in the two groups. Results：The total effective rate in the treatment group was higher than that in the control group (P＜0.05). In the two groups，TCM syndrome scores，FSS scores，and each domain of SF- MPQ [Pain Rating Index (PRI)， Visual Analogue Scale (VAS)， Present Pain Intensity (PPI)] after treatment were lower than those before treatment (P＜0.05)， and the TCM syndrome scores， FSS scores，and each dimension of SF-MPQ [PRI，VAS，PPI] in the treatment group were lower than those in the control group (P＜0.05). No adverse reactions occurred in the two groups. Conclusion： Micro acupotomy combined with Multivitamin and Minerals Tablets for chronic fatigue syndrome can significantly relieve fatigue and pain symptom of patients with high safety.