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Aims and objectives To develop a Chinese version of the human immunodeficiency virus–related Fatigue Scale and examine its reliability and validity. Background Fatigue is found in more than 70% of people infected with human immunodeficiency virus. However, a scale to assess fatigue in human immunodeficiency virus–positive people has not yet been developed for use in Chinese-speaking countries. Design A methodologic study involving instrument development and psychometric evaluation was used. Methods The human immunodeficiency virus–related Fatigue Scale was examined through a two-step procedure: (1) translation and back translation and (2) psychometric analysis. A sample of 142 human immunodeficiency virus–positive patients was recruited from the Infectious Disease Outpatient Clinic in central Taiwan. Their fatigue data were analysed with Cronbach's α for internal consistency. Two weeks later, the data of a random sample of 28 patients from the original 142 were analysed for test–retest reliability. The correlation between the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus and the Chinese version of the human immunodeficiency virus-related Fatigue Scale was analysed for concurrent validity. The Chinese version of the human immunodeficiency virus–related Fatigue Scale scores of human immunodeficiency virus–positive patients with highly active antiretroviral therapy and those without were compared to demonstrate construct validity. Results The internal consistency and test–retest reliability of the Chinese version of the human immunodeficiency virus–related Fatigue Scale were 0·97 and 0·686, respectively. In regard to concurrent validity, a negative correlation was found between the scores of the Chinese version of the human immunodeficiency virus–related Fatigue Scale and the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus. Additionally, the Chinese version of the human immunodeficiency virus–related Fatigue Scale could be used to effectively distinguish fatigue differences between the human immunodeficiency virus–positive patients with highly active antiretroviral therapy and those without. Conclusions The Chinese version of the human immunodeficiency virus–related Fatigue Scale presents good reliability and validity through a robust psychometric analysis. This scale can be appropriately applied to human immunodeficiency virus–positive patients by clinical staff and case managers in Chinese-speaking countries. Relevance to clinical practice The Chinese version of the human immunodeficiency virus–related Fatigue Scale is an effective and comprehensive tool that can help clinical professionals measure the frequency, strength and impact on the quality of life of fatigue in Chinese human immunodeficiency virus–positive patients.