Objective To explore the correlation and diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in peripheral blood of patients with exacerbation of chronic obstructive pulmonary disease (COPD). Methods One hundred patients with acute exacerbation of COPD who were hospitalized in the hospital between January 2019 and October 2020 were selected as exacerbation group, and another 100 patients with stable COPD who received treatment during the same time period were enrolled as stable group. The general data of patients were collected, and blood samples were collected to detect hemoglobin (Hb), platelet count (PLT), white blood cell count (WBC), neutrophil count, lymphocyte count and RDW, and the NLR was calculated. The correlation between the detection indicators was analyzed and receiver operating characteristic (ROC) curve was drawn to analyze the detection significance of related indicators. Results There were no statistical differences in the levels of Hb and PLT between the exacerbation group and the stable group (P>0.05). The levels of WBC, NLR, RDW and high-sensitivity C-reactive protein (hs-CRP) in the exacerbation group were significantly higher than those in the stable group (all P<0.05). NLR in the patients with acute exacerbation of COPD was positively correlated with serological indicators of WBC and hs-CRP (all P<0.05). ROC curve showed that the sensitivity and specificity of NLR in the diagnosis of acute exacerbation of COPD were 92.0% and 68.0% respectively, those of RDW were 91.0% and 58.0% respectively, those of hs-CRP were 77.0% and 71.0% respectively, and those of NLR+RDW were 90.0% and 73.0% respectively. NLR had the highest diagnostic specificity, RDW had the highest diagnostic sensitivity, and NLR+RDW had the best diagnostic efficiency. Conclusions Serological indicators of WBC, hs-CRP, NLR and RDW in patients with acute exacerbation of COPD will be abnormally increased, and NLR has a positive correlation with WBC and hs-CRP. NLR and RDW have high specificity and high sensitivity respectively in the diagnosis of patients with exacerbation of COPD, and their detection can strengthen the diagnosis and mastery of disease in patients.