Fatigue is a subjective, unpleasant, potentially disabling symptom rooted in physiological, psychological, and behavioral causes. People living with HIV are a population highly affected by fatigue due to risk factors associated with HIV-infection, treatment, and psychosocial disease burden. People with HIV are living longer, and are facing the challenge of a longer disease trajectory. Palliative nurses with expertise in symptom management can play a crucial role in helping people with HIV to engage in health behaviors that prevent or mitigate fatigue. In this paper we present a definition and overview of fatigue, describe the problem of fatigue in people living with HIV, and present a case study that illustrates the role of the palliative nurse in helping a person with HIV to cope with fatigue. Fatigue Fatigue is a subjective, unpleasant, potentially disabling symptom characterized by physical and/or psychological exhaustion, experienced both acutely and chronically, that results impaired function. 1,2 In states of fatigue, individuals experience an imbalance between their available physical and psychological resources and the resources required for optimal functioning. 2 Fatigue has been associated with depression, chronic disease states, prolonged exertion, stress, sleep disturbance and inactivity. 2 Although fatigue is often discussed in the context of physical weakness and sleepiness, 2 it is a multidimensional symptom that also impacts judgment, decision-making, motivation, and awareness. 3 Fatigue in People Living with HIV Fatigue affects nearly 90% of PLWH 3 and has been reported as one of the most persistent and troubling symptoms they experience. While a direct link between HIV and fatigue remains elusive, 3 PLWH have an elevated risk of fatigue related to hematologic and metabolic changes that are a direct result of HIV infection and treatment, as well as psychological and psychosocial stressors that have been linked with high fatigue symptom burden 2,4,5 (Figure 1). Physiological Factors Anemia (generally defined as hemoglobin [Hgb] <13 in men; <12 in women] is common in PLWH, affecting more than 70% of individuals diagnosed. 4,6 Anemia in PLWH is multifactorial and can be caused by chronic inflammation, medication side effects,