Background: Vitamin D (VD) has a coordinated immune function. Decreased VD levels are closely related to the occurrence of post-COVID-19 Conditions (PCC), but the specific mechanism is still unclear. Methods: We collected 50 PCC patient serum samples and divided them into three groups by different VD levels: VD sufficient group (VD ≥ 30 ng/mL), VD insufficient group (20 ng/mL ≤ VD < 30 ng/mL), VD deficiency group (VD < 20 ng/mL) and then subjected to proteomic analysis. Results: We identified 15 differential abundance proteins (DAPs) between the VD sufficient and VD insufficient groups, among which 11 DAPs were up-regulated and 4 DAPs were down-regulated in the VD insufficient group, including 5 immunoglobulin proteins (JCHAJN, IGHV4-28, GHV4-34, IGHM, and IGLV2-11), a complement component C7, and CD5L. Except for C7, the remaining 6 DAPs were significantly negatively correlated with VD levels in PCC patients. These DAPs were primarily enriched in immune-related pathways such as TNF signaling pathway and B cell receptor signaling pathway. Moreover, compared with the VD insufficient group, VD deficiency resulted in an abnormal abundance of 12 proteins, of which 4 proteins were up-regulated and 8 proteins were down-regulated, such as VD deficiency leads to a declined abundance of IGLV1-47 negatively correlated with serum VD levels. These 12 DAPs were also broadly involved in immune-related pathways. Furthermore, we found that ALB was in the center of the PPI network map of all DAPs and was negatively correlated with serum VD levels. Conclusion: VD insufficient/deficient leads to abnormalities in immunoglobulin heavy, light, and J chains, resulting in immune system dysfunction leading to PCC syndrome. VD supplementation may be a potential therapeutic strategy to alleviate the symptoms of PCC.