Vitamin D (VD) levels are closely related to the occurrence of post-COVID-19 conditions (PCCs), but the specific mechanism is still unclear. Here, a total of 50 PCC patient serum samples were divided into the VD sufficient group (VD ≥ 30 ng/mL), the VD insufficient group (20 ng/mL ≤ VD <
30 ng/mL), and the VD deficiency group (VD <
20 ng/mL) and then subjected to proteomic analysis. We identified 15 differential abundance proteins (DAPs) between the VD sufficient and VD insufficient groups, including 5 immunoglobulin proteins (JCHAJN, IGHV4-28, GHV4-34, IGHM, and IGLV2-11), which were significantly negatively correlated with VD levels in PCC patients. These DAPs were primarily enriched in immune-related pathways such as the TNF signaling pathway and the B cell receptor signaling pathway. Compared with the VD insufficient group, VD deficiency resulted in 4 proteins being upregulated and 8 proteins being downregulated. The declined abundance of IGLV1-47 negatively correlated with serum VD levels. Albumin (ALB) was in the center of the protein-protein interaction (PPI) network map of all DAPs and was negatively correlated with serum VD levels. In conclusion, VD insufficiency/deficiency leads to abnormalities in immunoglobulin heavy, light, and J chains, resulting in PCC syndrome. VD supplementation may be a potential therapeutic strategy to alleviate the symptoms of PCC.