Introduction: Increased red blood cell distribution width (RDW) has been reported to be related to underlying chronic inflammation. Our aim is to investigate the relationship of different complete blood count (CBC) parameters such as hemoglobin level, mean corpuscular volume (MCV), mean platelet volume (MPV) or RDW with COPD exacerbation severity. Methods: In the present retrospective analysis, consecutive patients admitted with the diagnosis of “COPD Exacerbation” between 1 January 2012 and 31 December 2015 were evaluated. Results: The study population included 804 patients with COPD exacerbation. The maximal partial pressure of carbon dioxide in the arterial blood (PaCO2) during hospital stay was significantly higher in patients with high MCV (p< 0.001), and in patients with a high RDW (p< 0.001). The hospitalization duration was significantly longer in patients with high RDW (p< 0.001) and in patients with elevated C-reactive protein (CRP) levels (p< 0.001). CRP levels strongly correlated to RDW (p= 0.001). Conclusions: Our study demonstrated that different CBC parameters, such as MCV and RDW, are in correlation with the severity of acute exacerbation of COPD reflected by the PaCO2level and the duration of hospitalization. Furthermore, we also found a positive correlation between RDW and CRP levels. This finding supports the hypothesis that RDW is a good biomarker of acute inflammation.