Fatigue is a frequently reported symptom by persons with HIV infection and one that has an adverse impact on activities of daily living and overall quality of life. Although the concept of fatigue has been studied extensively and discussed in the literature, little is known about the experience of fatigue by persons with HIV infection. A hermeneutic phenomenological study was conducted to investigate the subjective experience of HIV-associated fatigue and to describe the management of fatigue in the context of daily life. In-depth interviews were done with 10 adult patients of an outpatient HIV/AIDS clinic. Thematic analysis identified three concerns that represented the meaning of fatigue for the participants. The first concern was ‘Fatigue as a signal of AIDS’. A second concern was ‘The mind, the body, the social experience of fatigue’. The third concern was ‘Choosing ways to live with fatigue and addiction’. The findings provide insights for nursing practice regarding the subjective meaning of fatigue for patients with HIV and the need for nurses to explore this topic with patients.