SummaryCardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and nonsystematic reviews have increasingly reported autonomic function impairment in these subjects. For a better understanding, this systematic review was performed to evaluate not only the evidence for autonomic function impairment, but also factors influencing it. The results of the studies reviewed showed a strong level of evidence to support the impairment of heart rate variability in the time domain. A similar evidence level was also found to support impairment in baroreceptor sensitivity and muscle sympathetic nerve activity. Furthermore, this review identified physical activity level, muscle function, and circadian rhythm as the major influencing factors (strong evidence) of autonomic function in subjects with COPD. However, no definite conclusion could be reached for factors such as dyspnea, anxiety, body composition, pulmonary function, age, breathing frequency, ventilatory effort, quality of life, and disease severity due to limited, conflicting, or lack of existing evidence. The results of this review highlight relevant clinical messages for clinicians and other health-care providers regarding the role autonomic function can play as an important physiological marker for prognostication and stratification. Hence, autonomic function outcomes should be identified and considered during management of patients with COPD. Moreover, this review can serve as basis for future research aimed at assessing the interventions for autonomic function abnormalities in these patients.