Chronic obstructive pulmonary disease (COPD) is characterized by progressive pulmonary and systemic inflammation. Acute exacerbations of COPD (AECOPD) are associated with acute inflammation and infections and increase the rates of morbidity and mortality. Currently, neither the aetiology nor pathogenesis of AECOPD are entirely understood. Exosomes have been reported to regulate immunity and inflammation via specific intercellular communications through an array of macromolecules (e.g. microRNA and proteins) contained within these microvesicles. We evaluated the level of circulating exosomes in relation to systemic inflammation in patients with AECOPD (n = 20) or stable COPD (sCOPD; n = 20) in comparison to non-smoking healthy controls (n = 20). Exosomes in plasma were isolated by precipitation-based method, and quantified using a CD9 expression based enzyme-linked immunosorbent assay (ELISA). Plasma biomarkers of systemic inflammation, C-reactive protein (CRP), soluble tumour necrosis factor receptor-1 (sTNFR1) and interleukin (IL)-6 were also quantified using ELISA. Levels of plasma exosome were higher in AECOPD patients (p < 0.001) and sCOPD patients (p < 0.05) compared to controls. Plasma levels of CRP and sTNFR1 were highest in AECOPD, followed by sCOPD patients compared to healthy controls (p < 0.05). Plasma IL-6 was elevated in AECOPD (p < 0.05) and sCOPD patients (p < 0.01) compared to controls. The level of exosome correlated with the levels of CRP, sTNFR1 and IL-6 in plasma. Exosomes may therefore be involved in the inflammatory process of AECOPD. Further studies involving exosomal phenotyping and molecular characterization are required to fully understand their role in the pathophysiology of COPD.