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Natalia Troianova,1,* Barbara Mariotti,1,* Valentina Micheletti,2,3 Federica Calzetti,1 Marta Donini,1 Gianluca Salvagno,4,5 Marcello Ferrari,2,3 Ernesto Crisafulli,2,3 Flavia Bazzoni1 1Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy; 2Department of Medicine, Respiratory Medicine Unit, University of Verona and Verona University Hospital, Verona, Italy; 3Department of Medicine, Section of Internal Medicine, University of Verona and Verona University Hospital, Verona, Italy; 4Section of Clinical Biochemistry, University Hospital of Verona, Verona, Italy; 5Service of Laboratory Medicine, Pederzoli Hospital, Peschiera del Garda, Italy*These authors contributed equally to this workCorrespondence: Flavia BazzoniDepartment of Medicine, Division of General Pathology University of Verona, Strada le Grazie 8, Verona, 37134, ItalyTel +39 045 8027128Email flavia.bazzoni@univr.itPurpose: Chronic obstructive pulmonary disease is characterized by chronic inflammatory response both at the lung site and at the systemic level. Abnormalities in circulating leukocytes have been reported to occur in COPD patients and have been often shown to correlate with the decline in lung function. COPD affects men and women at a virtually comparable rate, even though distinct sex specific symptoms, progression and therapeutic implications have been described. Nonetheless, these sex-associated differences have not been analyzed in terms of circulating leukocytes. To assess the impact of sex on the changes of circulating immune cells in COPD patients.Patients and Methods: Blood samples were collected from 50 COPD patients (31 males, 19 females) and 63 age and sex-matched controls (35 males, 28 females) enrolled in this pilot study. Complete blood cell count and multi-parametric flow cytometry analysis were performed to characterize the leukocyte populations and subsets.Results: Male COPD patients are distinguished from controls by a significant increase in white blood cell counts, neutrophil total and differential counts, and neutrophil-to-lymphocyte ratio. Conversely, a generalized leukocyte decrease discriminated female COPD patients from the related controls. The impact of sex is further remarked by a decrease in adaptive immune cell subpopulations in males as opposed to a consistent increase of innate immune cell types in females correlating with disease severity.Conclusion: These data indicate that the definition of specific changes of circulating leukocytes to be used as reliable biomarkers of the disease severity cannot be accomplished irrespectively of sex.Keywords: sex, COPD, blood leukocytes, neutrophil-to-lymphocyte ratio, neutrophilia