Chronic obstructive pulmonary disease (COPD) is a result of inflammation and/or alterations in repair mechanisms, the “release” of inflammatory mediators into the bloodstream can lead to important systemic manifestations of the disease. Systemic inflammation aggravates comorbidities (ischemic heart disease, heart failure, osteoporosis, normocytic anemia, lung cancer, depression, diabetes). Comorbidities increase the incidence of COPD, lead to increased hospitalizations, mortality and health care costs. They complicate the management of COPD and require careful assessment. There are two points of view on the relationship between systemic manifestations and comorbidities of COPD. For many, manifestations are the result of a systemic “spillover” of inflammatory processes occurring in the lungs of patients with COPD, with the disease remaining the center of the process. Whereas for others, the pulmonary manifestations of COPD are another form of expression of a “systemic” inflammatory condition with damage to many organs. Both perspectives have merit but have different therapeutic implications. The first focuses on the lungs, while the second focuses on systemic inflammation. It is clear that the next decade will see an explosion of information attempting to clarify the links between COPD and its systemic manifestations, provide evidence of mechanisms, and improve patient management. The distinction between systemic manifestation and comorbidity is difficult to define, and the authors of this review consider them together