Background: Patients with human immunodeficiency virus (HIV) infection would face the progressing of illness, the pressure of the disease per se and its related medications. Therefore, more than 70% patients suffered from fatigue. Once the symptoms of fatigue appear, the self-care ability and the daily activity of HIV-infected patients would be disturbed. However, there is still no scale to measure fatigue for HIV infected patients up to now. Purpose: To develop the Chinese Version of HIV-related Fatigue Scale (C-HRFS) using two-way translation and tests of reliability and validity. Method: Two steps are included in this study: First, the English-Chinese inter-translation was evolved to develop C-HRFS. Second, the psychometric analysis of C_HRFS was performed. The participants were recruited from an Infectious Disease Outpatient Clinics at a medical center in centeral Taiwan. The data collected for a total of 118 HIV-infected patients were analyzed using Cronbach’ α, indicating internal consistency. After two weeks, the same data of 28 patients were collected again to perform the analysis of the test-retest reliability. The correlation of World Health Organization Quality of Life Assessment-HIV (WHOQOL-HIV) and C-HRFS were examined to indicate the concurrent validity. The difference of the C-HRFS scores between the groups of with or without highly active antiretroviral therapy (HAART) was examined to indicate the construct validity. Result: It was demonstrated that C-HRFS showed a good English-Chinese translation equivalence. The Cronbach's α was 0.97, and the test-retest reliability was 0.686 ( p <0.01). C-HRFS was negatively related to the WHOQOL-HIV (r=-0.64, p <0.01).The C-HRFS scale scores of the HIV patients with HAART were significantly higher than that of the HIV patients without (p <0.01). Conclusions: C-HRFS has good reliability and validity, and the process of the psychometric analysis was rigorous. It can be used in Taiwanese HIV patients. However, the four alleviating factors of the fatigue subscales were not suggested to be used in follow-ups on HIV-infected patients with fatigue in Taiwan. Accordingly, C-HRFS provides clinical practitioners and case management personnel with an useful evaluation tool.