Purpose Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow limitation and systemic inflammation. Recently, there has been growing interest in adipose tissue-mediated inflammation in the pathogenesis of COPD. The aim of our study was to determine the relationships between a new adipocytokine, meteorin-like protein (Metrnl), and acute exacerbations of COPD, smoking, and comorbidities. Materials and Methods The study included 313 patients aged 40-65 years in four groups: Group 1: ex-smokers (>= 20 pack-years) with COPD hospitalized for COPD exacerbation (n = 133), Group 2: current-smokers (>= 20 pack-years) without COPD (n = 60), Group 3: ex-smokers (>= 20 pack-years) without COPD (n = 60), and Group 4: never-smokers without COPD (n = 60). Peripheral venous blood samples (5 cc) were collected from all participants. Plasma Metrnl levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit. Results Mean Metrnl levels were 28.45 +/- 11.27 ng/ml in Group 1, 24.34 +/- 4.38 ng/ml in Group 2, 18.84 +/- 3.8 ng/ml in Group 3, and 19.44 +/- 3.92 ng/ml in Group 4. Group 1 had significantly higher mean Metrnl level compared to the other groups (p = 0.006, p = 0.001, p = 0.001). Metrnl level was also significantly higher in Group 2 when compared with Groups 3 and 4 (p = 0.001, p = 0.005). Group 1 patients with diabetes mellitus and coronary artery disease showed significantly lower Metrnl levels compared to other patients in the group (p = 0.001, p = 0.001). Conclusion The high Metrnl level in COPD exacerbations and active smoking may be important in balancing the inflammatory response. However, plasma Metrnl levels were found to be lower in COPD patients with comorbidities.