Objective To analyze the values of peripheral blood red blood cell distribution width (RDW), neutrophil (NEU) to lymphocyte (LYM) ratio (NLR), fibrinogen (FIB) to albumin (ALB) ratio (FAR) and surfactant protein A (SP-A) in evaluating patient condition and risks of acute exacerbation of COPD. Methods A total of 200 patients with COPD admitted to Hebei University Affiliated Hospital from January 2021 to December 2023 were selected as study subjects. All the patients had follow-up visits in the outpatient department within the past three months. According to the presence or absence of acute exacerbation, they were divided into exacerbation group (n = 96) and non-exacerbation group (n = 104). Meanwhile, 50 healthy volunteers were assigned to a control group. Peripheral blood RDW, NEU, LY, FIB, ALB and SP-A in the three groups were compared. NLR and FAR were calculated. The correlation of RDW, NLR, FAR, and SP-A with the severity of AECOPD was analyzed. ROC curves were used to analyze the values of RDW, NLR, FAR, and SP-A in evaluating the risks of acute exacerbation of COPD. Multivariate logistic regression analysis was conducted to identify the risk factors for AECOPD. The differences in RDW, NLR, FAR, and SP-A were compared among the patients with different prognoses. Results Peripheral blood RDW, NEU, NLR, FIB, FAR and SP-A were higher in the exacerbation group than in the non-exacerbation group, whereas LYM and ALB were lower (P < 0.05). Levels of RDW, NLR, FAR and SP-A were higher in the patients with grade Ⅲ AECOPD than those with grade Ⅱ or grade Ⅰ AECOPD (P < 0.05). RDW, NLR, FAR, SP-A, and grade of patient condition in patients with AECOPD were positively correlated in pairs (P < 0.05). The sensitivity, specificity and area under the ROC curve of combined prediction of AECOPD using RDW, NLR, FAR and SP-A were 0.798 and 0.830 (95% CI: 0.738 ~ 0.922), all of which were superior to prediction using a single indicator. Multivariate analysis found that smoking, RDW > 14.33%, NLR > 2.80, FAR > 0.08, and SPA > 2.21 ng/mL were risk factors for acute exacerbation of COPD (P < 0.05). RDW, NLR, FAR, and SP-A in the readmission group within 30 days after discharge were higher than those in the non-readmission group (P < 0.05). Conclusions RDW, NLR, FAR, and SP-A are closely related to the patient condition of COPD, and can help to predict the risk of acute exacerbation and prognosis. Therefore, they are worthy of monitoring in clinical practice. [ABSTRACT FROM AUTHOR]