Chronic obstructive pulmonary disease (COPD) is characterized by small airways, alveolar and systemic inflammation and remodeling causing airflow limitation and parenchymal destruction. Mechanisms of oxidative stress include exposure to cigarette smoke and environmental stimuli that activate proinflammatory responses, stimulate alveolar neutrophils and macrophages and lead to apoptosis of endothelial and epithelial cells. COPD may have origins in fetal and neonatal factors that affect intrauterine growth of lungs and airways, lead to low birth weight and impair the development of immune response. Maternal smoking may diminish interferon response secondary to micronutrient deficiency, particularly of Vitamin A, and support persistence of Respiratory Syncytial Virus (RSV), normally a childhood pathogen, into adult life. Muscle wasting and cachexia are systemic features of COPD. Cachexia is associated with systemic inflammation and worsened by Vitamin D deficiency. Nutritional depletion is related to poor survival and is a rational target for therapeutic intervention in advanced and critically ill patients. Preliminary studies and suggest that supplementation with omega-3 polyunsaturated fatty acids and micronutrient repletion with Vitamin A, Vitamin D3, and zinc may have beneficial effects in COPD.