Chronic obstructive pulmonary disease (COPD) is a growing global health burden, with mortality rates underestimated due to difficulty in identifying the exact cause of death. Respiratory failure is the major cause of death in advanced COPD, while cardiovascular disease and lung cancer are also significant contributors, especially in mild-to-moderate cases. The link between COPD and these conditions is likely through systemic and pulmonary inflammation, which is a known risk factor for cardiovascular disease and cancer. Lung function measurements like FEV1 predict mortality in COPD, but composite tools such as the BODE index, which incorporates BMI, airflow obstruction, dyspnea, and exercise capacity, predict mortality better. These tools reflect the range of comorbidities and underlying mechanisms in COPD. COPD is associated with numerous comorbidities, including cardiovascular disease, lung cancer, and osteoporosis. Studies show that COPD patients have a higher risk of comorbidities compared to controls. The Charlson Index, a tool to quantify comorbidities, is used to assess mortality risk in COPD patients. However, its relationship with mortality is not linear, and its predictive value may be limited. Cancer and cardiovascular disease are the two most significant comorbidities in COPD mortality. COPD patients with these conditions have higher mortality rates. The relationship between COPD and these comorbidities is likely due to systemic and pulmonary inflammation. COPD is an independent risk factor for lung cancer, with chronic bronchitis and emphysema increasing the risk. Chronic inflammation may also contribute to the development of lung cancer. COPD is also linked to cardiovascular disease, with increased risk of heart failure, arrhythmias, and acute myocardial infarction. Reduced FEV1 is a marker for cardiovascular mortality. Systemic inflammation is a key factor in atherosclerosis, and COPD patients have elevated levels of inflammatory markers such as CRP and TNF-α, which may contribute to cardiovascular mortality. Comorbidities play a significant role in COPD mortality, and their impact is often underestimated. Future research should focus on standardizing the reporting of causes of death in COPD, standardizing ICD codes for COPD, and considering comorbidities in clinical trials. Health status tools like the BODE index and SGRQ are better predictors of mortality than FEV1 alone. All-cause mortality should be a primary endpoint in future COPD studies. Current evidence supports the use of supplemental oxygen and smoking cessation in COPD patients, but more research is needed to evaluate other therapies. COPD is a complex disease with serious comorbidities, and future studies should consider it as a multicomponent disease with systemic and pulmonary inflammation at its core.Chronic obstructive pulmonary disease (COPD) is a growing global health burden, with mortality rates underestimated due to difficulty in identifying the exact cause of death. Respiratory failure is the major cause of death in advanced COPD, while cardiovascular disease and lung cancer are also significant contributors, especially in mild-to-moderate cases. The link between COPD and these conditions is likely through systemic and pulmonary inflammation, which is a known risk factor for cardiovascular disease and cancer. Lung function measurements like FEV1 predict mortality in COPD, but composite tools such as the BODE index, which incorporates BMI, airflow obstruction, dyspnea, and exercise capacity, predict mortality better. These tools reflect the range of comorbidities and underlying mechanisms in COPD. COPD is associated with numerous comorbidities, including cardiovascular disease, lung cancer, and osteoporosis. Studies show that COPD patients have a higher risk of comorbidities compared to controls. The Charlson Index, a tool to quantify comorbidities, is used to assess mortality risk in COPD patients. However, its relationship with mortality is not linear, and its predictive value may be limited. Cancer and cardiovascular disease are the two most significant comorbidities in COPD mortality. COPD patients with these conditions have higher mortality rates. The relationship between COPD and these comorbidities is likely due to systemic and pulmonary inflammation. COPD is an independent risk factor for lung cancer, with chronic bronchitis and emphysema increasing the risk. Chronic inflammation may also contribute to the development of lung cancer. COPD is also linked to cardiovascular disease, with increased risk of heart failure, arrhythmias, and acute myocardial infarction. Reduced FEV1 is a marker for cardiovascular mortality. Systemic inflammation is a key factor in atherosclerosis, and COPD patients have elevated levels of inflammatory markers such as CRP and TNF-α, which may contribute to cardiovascular mortality. Comorbidities play a significant role in COPD mortality, and their impact is often underestimated. Future research should focus on standardizing the reporting of causes of death in COPD, standardizing ICD codes for COPD, and considering comorbidities in clinical trials. Health status tools like the BODE index and SGRQ are better predictors of mortality than FEV1 alone. All-cause mortality should be a primary endpoint in future COPD studies. Current evidence supports the use of supplemental oxygen and smoking cessation in COPD patients, but more research is needed to evaluate other therapies. COPD is a complex disease with serious comorbidities, and future studies should consider it as a multicomponent disease with systemic and pulmonary inflammation at its core.