OBJECTIVE: This study aimed to assess the predictive value of the neutrophil-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), and serum amyloid A (SAA) in predicting acute exacerbations of chronic obstructive pulmonary disease (AECOPD) complicated by respiratory failure (RF). METHODS: A retrospective study was conducted on 198 patients with AECOPD in the Respiratory Department of No. 2 People's Hospital of Fuyang City from December 2022 to May 2023. Patients were categorized into two groups: an experimental group with the presence of RF (n = 70) and a control group with no RF present (n = 128). Baseline characteristics and inflammatory marker levels were compared between the two groups, and their impact on the risk of readmission within one year was analyzed to assess the predictive value of NLR, CAR, and SAA in patients with AECOPD and RF. RESULTS: The experimental group exhibited significantly higher levels of white blood cells, neutrophils, C-reactive protein (CRP), SAA, NLR, and CAR compared to the control group. Additionally, the experimental group had a higher one-year readmission rate, with statistically significant differences. The areas under the receiver operating characteristic (ROC) curve for NLR, CAR, and SAA in predicting AECOPD with RF were 0.705, 0.659, and 0.656, respectively. When combined, the ROC area under the curve for these three markers increased to 0.717, which was statistically significant. CONCLUSION: The combined assessment of NLR, CAR, and SAA offers a reliable reflection of systemic inflammation and holds predictive value for AECOPD with RF.