Chronic obstructive pulmonary disease (COPD) constitutes a set of heterogeneous symptoms affecting millions of people worldwide. The associated comorbidities developing in COPD involve dysregulation in physiological pathways resulting from systemic inflammation in respiratory airways. In addition to mentioning the pathophysiology, stages, and consequences of COPD, this paper also defines red blood cell (RBC) indices such as hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cell distribution width, and RBC count. It explains the role of RBC indices and RBC structural abnormalities with disease severity and exacerbations in COPD patients. Although many factors have been studied as a marker of morbidity and mortality for COPD patients, RBC indices have emerged as revolutionary evidence. Therefore, the effectiveness of evaluating RBC indices in COPD patients and their importance as a negative predictor of survival, mortality, and clinical outcomes have been debated through rigorous literature reviews. Furthermore, the prevalence, mechanisms of development, and prognosis of underlying anemia and polycythemia in COPD have also been evaluated, with anemia most significantly associated with COPD. Therefore, more studies should be conducted to address underlying anemia in COPD patients to lessen the severity and disease burden. Correcting the RBC indices in COPD patients remarkably impacts the quality of life and reduces in-patient admissions, healthcare resource utilization, and costs. Hence, it is noteworthy to understand the significance of considering RBC indices while dealing with COPD patients.