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ABSTRACT Infection is a major cause of mortality in chronic kidney disease (CKD) patients. Although immune dysfunction is a risk factor for infection in CKD patients, its causes are not fully elucidated. In the present study, we evaluated whether p‐cresyl sulfate (pCS), an intestinal bacteria‐derived uremic toxin, was involved in immune dysfunction in CKD. We used osmotic pumps to establish adenine‐induced renal dysfunction mice with a chronically high blood pCS concentration. Analysis of lymphocyte subsets revealed that pCS significantly reduced peripheral B cells in renal dysfunction mice. In vitro, pCS inhibited interleukin (IL)‐7‐induced proliferation of CD43+ B‐cell progenitors and suppressed IL‐7‐induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) in these cells. Cell cycle analysis showed that pCS significantly decreased the percentage of CD43+ B‐cell progenitors in S phase and increased that in G1 phase. These results suggest that pCS suppressed IL‐7‐induced STAT5 signaling and inhibited B‐cell progenitor proliferation, leading to reduction of peripheral B cells in adenine‐induced renal dysfunction mice. Therefore, pCS decreases peripheral B cells by inhibiting proliferation of CD43+ B‐cell progenitors and is a likely cause of immune dysfunction in CKD patients. HighlightsRenal dysfunction mice with high blood p‐cresyl sulfate (pCS) were established.pCS significantly reduced peripheral B and NK cells in renal dysfunction mice.pCS inhibited IL‐7‐induced proliferation of B‐cell progenitors.pCS suppressed IL‐7‐induced phosphorylation of STAT5 in B cell progenitors.pCS decreased the percentage of B‐cell progenitors in S phase.