B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE). BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs). Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p