© 2020 Elsevier Inc.Background: Chronic obstructive pulmonary disease (COPD) comprises a significant number of emergency department (ED) presentations, and hematological phenotypes may have prognostic significance. The aim of this study was to investigate the effect of hematological phenotypes on serious outcomes in COPD exacerbations. Methods: A prospective cohort study was carried out in patients with COPD exacerbation presenting to the ED. The patients were classified into three groups, including neutrophilic, eosinophilic, and mixed-type (including neutrophilic and eosinophilic features) COPD exacerbation. Outcome measures were defined as mortality, hospitalization, and need for intensive care unit (ICU) care within three months, and these outcomes were compared among groups. Results: A total of 173 COPD patients were assessed for eligibility, and 147 of them were included in the final analysis. The study population consisted of 90 patients with neutrophilic exacerbation (61.2%), 26 patients with eosinophilic exacerbation (17.7%), and 31 patients with mixed-type exacerbation (21.1%). The neutrophilic exacerbation group was older, was more often tachycardic and desaturated, and had more sputum production compared with the eosinophilic exacerbation group. Mortality was seen in 35 patients in the neutrophilic exacerbation group (38.9%), whereas 5 patients in the eosinophilic group (19.2%) and 6 patients in the mixed-type group (19.4%) died (p = .044). No difference was observed among groups in terms of hospital and ICU admission. Conclusion: COPD exacerbations with neutrophilic phenotypes presented to the ED with more serious clinical findings compared with eosinophilic exacerbations. This may also have a possible effect on mortality.