Objective To analyze the composition of known plasmacytosis in systemic lupus erythematosus (SLE) to obtain further insight into the nature of underlying mechanisms. Methods Plasmablasts from patients with active SLE, patients with inactive/treated SLE, and healthy controls were characterized by flow cytometry, enzyme‐linked immunospot assay, and Transwell migration assays and compared to vaccination‐induced plasmablasts. Serum cytokine levels were analyzed by Luminex assay, and histologic analysis of kidney biopsy specimens was performed. Results Circulating plasmablasts in SLE expressed markers of mucosal immune reactions. IgA, CCR10, and β7 integrin were expressed by 48%, 40%, and 38% of plasmablasts, respectively, with varying coexpression patterns. Consistent with mucosal homing, some SLE plasmablasts migrated toward the mucosal chemokine CCL28 and secreted polymeric IgA. SLE plasmablasts shared phenotypic characteristics with antigen‐specific plasmablasts induced by oral, but not parenteral, vaccinations. Autoreactive antibody–secreting cells of the IgG and IgA isotypes were detectable, but only the emergence of phenotypically mucosal plasmablasts was positively associated with serum interleukin‐2 and platelet‐derived growth factor BB levels. Conclusion Our data suggest that distinct plasmablast differentiation pathways jointly contribute to peripheral plasmacytosis in SLE, i.e., a cytokine‐amplified mucosal “steady‐state” plasmablast response, and an autoreactive plasmablast response, representing conventional autoimmunity. Our results indicate an overly activated mucosal immune system in patients with SLE, with both immunologic and clinical implications.