Long-lived plasma cells (LLPCs) reside in bone marrow (BM) and provide antibodies for a long time to defend against infection. LLPCs are retained in niches which are composed of several myeloid cells and CXCL12+ stromal cells. However, the mechanism for the longevity of LLPCs is not fully understood. To explore the factors important for longevity of LLPCs, we performed gene expression analysis comparing LLPCs in BM with short-lived plasma cells (SLPCs) in spleen using microarray and microfluidic single-cell quantitative PCR. Single cell analysis revealed that LLPCs were clustered into several groups depend on their gene expression profiles. We found several genes including Secretory leukocyte peptidase inhibitor (SLPI) were highly expressed in LLPCs compared with SLPCs. SLPI is an protease inhibitor and an NF-κB signaling inhibitor. We verified that LLPCs abundantly produce SLPI proteins by ELISpot assay. IgG secretion was impaired in SLPI–/– PCs stimulated with IL-6 for 7 days compared with wild type PCs. These results suggest that SLPI is important for the function of plasma cells. It needs further investigation about the molecular mechanisms of SLPI for plasma cell longevity.