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Abstract Background Disease progression in COPD patient is associated to lung function decline, leading to a higher risk of hypoxaemia and associated comorbidities, notably cardiovascular diseases (CVD). Adiponectin (Ad) is an adipokine with cardio-protective properties. In COPD patients, conflicting results were previously reported regarding Ad plasmatic (Adpl) level, probably because COPD is a heterogeneous disease with multifactorial influence. Among these factors, gender and hypoxaemia could interact in a variety of ways with Ad pathway. Therefore, we postulated that these components could influence Adpl level and its multimers in COPD patients and contribute to the appearance of a distinct endotype associated to an altered CVD risk. Methods One hundred COPD patients were recruited: 61 were men and 39 were women. Patients who were not severely hypoxemic were allocated to non-hypoxemic group which included 46 patients: 27 men and 19 women. Hypoxemic group included 54 patients: 34 men and 20 women. For all patients, Adpl level and proportion of its different forms were measured. Differences between groups were evaluated by Rank-Sum tests. The relationship between these measures and BMI, blood gas analysis (PaO2, PaCO2), or lung function (FEV1, FEV1/FVC, TLCO, TLC, RV) were evaluated by Pearson correlation analysis. Results Despite similar age, BMI and obstruction severity, women had a higher TLC and RV (median: TLC = 105%; RV = 166%) than men (median: TLC = 87%; RV = 132%). Adpl level was higher in women (median = 11,152 ng/ml) than in men (median = 10,239 ng/ml) and was negatively associated with hyperinflation (R = − 0,43) and hypercapnia (R = − 0,42). The proportion of the most active forms of Ad (HMW) was increased in hypoxemic women (median = 10%) compared with non-hypoxemic women (median = 8%) but was not modulated in men. Conclusion COPD pathophysiology seemed to be different in hypoxemic women and was associated to Ad modulations. Hyperinflation and air-trapping in association with hypercapnia and hypoxaemia, could contribute to a modulation of Adpl level and of its HMW forms. These results suggest the development of a distinct endotypic presentation, based on gender.