Objective: To investigate the quantitative assessment efficacy of chest CT combined with serum Vanin-1 and SPP1 in determining the progression stage of chronic obstructive pulmonary disease (COPD). Methods: A total of 100 COPD subjects from our hospital from January 2020 to December 2023 were included and randomly divided into a healthy control group and an experimental group (50 cases each). The healthy control group underwent slow vital capacity measurement using a spirometer, while the experimental group underwent high-resolution thin-slice CT scans and serum Vanin-1 and SPP1 concentration measurements. Pulmonary function parameters, symptom burden, biomarker concentrations, and imaging characteristics were compared between the two groups. Results: The FEV1/FVC ratio in the experimental group (58.3 ± 7.2) was lower than that in the healthy control group (92.1 ± 4.8); the total CAT score (22.4 ± 3.5) was higher than that in the healthy control group (3.1 ± 1.2); both Vanin-1 (18.7 ± 2.3 μg/L) and SPP1 (25.6 ± 4.1 μg/L) levels were higher than those in the healthy control group; LAA%-950 (38.7 ± 6.2%) and WA% (68.5 ± 5.3%) were significantly higher than those in the healthy control group (all p < 0.001). Conclusion: Chest CT combined with serum Vanin-1 and SPP1 can accurately quantify the pathological progression of COPD, providing a dual basis for clinical staging and individualized intervention.