Introduction: Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations., Methods: Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators., Results: A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators., Conclusion: Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD., Competing Interests: Alexa Nuñez and Viviana Marras are co-first authors in this study. Alexa Nuñez is the recipient of a Rio Hortega contract in the 2019 Strategic Action Health Call from the Instituto de Salud Carlos III for the years 2020-2022. Viviana Marras from the University of Sassari (Italy) was the recipient of an Erasmus Placement for a short stay at the Pneumology Department of University Hospital Valld’Hebron (Barcelona, Spain). Miriam Barrecheguren is the recipient of a Rio Hortega contract in the 2017 Strategic Action Health Call from the Instituto de Salud Carlos III for the years 2018-2019. Matevz Harlander has received speaker or consulting fees from AstraZeneca, Berlin-Chemie, Menarini, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, all unrelated to this manuscript. Evgeni Mekov has received speaker or consulting fees from Astra Zeneca and Chiesi, all unrelated to this manuscript. Cristina Esquinas has received speaker fees from CSL Behring. Matjaz Turel has received speaker or consulting fees from AstraZeneca, Berlin-Chemie, Menarini, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, all unrelated to this manuscript. David Lestan has received speaker or consulting fees from Boehringer Ingelheim and Roche, all unrelated to this manuscript. Rosen Petkov has received speaker or consulting fees from Astra Zeneca and Boehringer Ingelheim, all unrelated to this manuscript. Nikolay Yanev has received speaker or consulting fees from Astra Zeneca, Boehringer Ingelheim, Berlin Chemie and Chiesi, all unrelated to this manuscript. Pietro Pirina has received speaker fees from Chiesi, Menarini, Novartis, Mundifarma, Glaxo Smith Kline, all unrelated to this manuscript. Marc Miravitlles has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Ferrer, Gebro Pharma, GlaxoSmithKline, Grifols, Kamada, Menarini, Mereo Biopharma, Novartis, pH Pharma, Rovi, Sanofi, Sandoz, TEVA, Verona Pharma and Zambon, and research grants from GlaxoSmithKline and Grifols, unrelated to this manuscript. Miriam Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK and consulting fees from GSK, Novartis and Gebro Pharma. The authors report no other conflicts of interest in this work., (© 2020 Nuñez et al.)