Immunoglobulin diversity includes B-cell receptor, T-cell receptor, and antibody diversity. Existing studies focus more on the role of B-cell and T-cell receptor diversity in tumor immunity, while little is known about antibody diversity. This study examined and compared the blood exosomes of lung cancer patients and healthy individuals via proteomics and bioinformatics analyses. The results showed that of the 270 identified proteins, those enriched in the defense mechanism items were the most abundant. Most were antibody subtype molecules, accounting for 50.00%. Similarly, of the 40 identified exosomal DEPs, 29 were enriched in the defense mechanism items (72.50%), with a higher proportion of antibody subtypes (82.76%). Furthermore, 24 DEP antibody molecules were involved in 18 immune reaction-related signaling pathways. These results indicated that human serum exosomes contained a large number of antibody molecules, while the antibody subtypes from the lung cancer serum exosomes differed from those of the healthy controls. The variation in antibody diversity may be closely related to LA tumor immunity.