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Millions of people worldwide have chronic obstructive pulmonary disease (COPD), and one of the most common and troublesome symptoms that must be managed is fatigue. While there are existing interventions to address COPD-related fatigue, not all patients experience benefit. A better understanding of the factors associated with COPD-fatigue could elucidate new approaches to address COPD-related fatigue, thereby offering relief to a greater number of patients. The purpose of this review was to identify the physiologic, psychologic, and situational factors associated with COPD-related fatigue. A total of four databases, PubMed, CINAHL, Scopus, and Google Scholar, were searched. Those that were peer reviewed, in English, and published between 2000 and 2021, were included in the review. A total of 25 articles were included in this scoping review. The following factors were related to fatigue in COPD: dyspnea, pain, anxiety, depression, and sleep. Fatigue is a debilitating symptom with factors influential to the symptom and outcomes. Research is indicated to explore targeted and personalized interventions addressing the factors related to fatigue to mitigate this widespread symptom.