Chronic obstructive pulmonary disease (COPD) is a complex condition characterized by airflow obstruction, which has profound systemic effects. Systemic inflammation, often initiated by pulmonary inflammation, can lead to various comorbidities such as skeletal muscle wasting, cachexia, osteoporosis, anaemia, and cardiovascular diseases. These comorbidities significantly increase the morbidity, mortality, and healthcare costs associated with COPD. The review discusses the mechanisms underlying these systemic manifestations, including the role of inflammatory mediators like interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and chemokines. It also highlights the importance of systemic inflammation in the progression of lung cancer and the potential benefits of anti-inflammatory treatments. The review further explores the impact of COPD on functional capacity, muscle dysfunction, and malnutrition, as well as the relationship between COPD and cardiovascular diseases, including coronary artery disease, heart failure, and pulmonary arterial hypertension. Additionally, it addresses the prevalence and management of normocytic anaemia, osteoporosis, and depression in COPD patients. The review emphasizes the need for comprehensive evaluation and management of comorbidities to improve the overall outcome for COPD patients.Chronic obstructive pulmonary disease (COPD) is a complex condition characterized by airflow obstruction, which has profound systemic effects. Systemic inflammation, often initiated by pulmonary inflammation, can lead to various comorbidities such as skeletal muscle wasting, cachexia, osteoporosis, anaemia, and cardiovascular diseases. These comorbidities significantly increase the morbidity, mortality, and healthcare costs associated with COPD. The review discusses the mechanisms underlying these systemic manifestations, including the role of inflammatory mediators like interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and chemokines. It also highlights the importance of systemic inflammation in the progression of lung cancer and the potential benefits of anti-inflammatory treatments. The review further explores the impact of COPD on functional capacity, muscle dysfunction, and malnutrition, as well as the relationship between COPD and cardiovascular diseases, including coronary artery disease, heart failure, and pulmonary arterial hypertension. Additionally, it addresses the prevalence and management of normocytic anaemia, osteoporosis, and depression in COPD patients. The review emphasizes the need for comprehensive evaluation and management of comorbidities to improve the overall outcome for COPD patients.