We conducted this study to characterize the relationship between primary Sjögren syndrome (pSS)-associated peripheral neuropathy (PN) and markers of B-cell monoclonal proliferation and chronic activation. The cohort included 120 consecutive patients presenting with definite pSS according to the American-European Consensus Group criteria. Serum markers of chronic B-cell activation included autoantibodies and hypergammaglobulinemia. Markers of monoclonal B-cell proliferation included mixed cryoglobulin, monoclonal gammopathy, abnormal κ/λ free light chain (FLC) ratio, and B-cell non-Hodgkin lymphoma (B-NHL). Definite PN was present in 30 patients (25%) including 7 patients (23%) with sensorimotor neuropathy, 3 patients (10%) with ataxic sensory neuropathy, and 20 patients (67%) with nonataxic sensory neuropathy. Patients with a sensorimotor neuropathy differed from those without PN by higher rates of monoclonal B-cell proliferation markers, that is, mixed cryoglobulin (57% vs. 11%; p = 0.008), monoclonal gammopathy (71% vs. 17%; p = 0.004), higher FLC ratio (2.7 ± 1.5 vs. 1.7 ± 1.8; p = 0.024), and B-NHL (57% vs. 3%; p < 0.001). Patients with nonataxic sensory neuropathy were characterized by a higher age (57.5 ± 10.7 vs. 48.7 ± 14.3 years; p = 0.007), more frequent central nervous system (CNS) involvement (15% vs. 2%; p = 0.04) and a lower prevalence of chronic B-cell activation serum markers, that is, antinuclear antibodies (ANA) (60% vs. 90%; p = 0.003), anti-SSA (Ro) (40% vs. 72%; p = 0.009), anti-SSB (La) (15% vs. 41%; p = 0.039), rheumatoid factor (37% vs. 67%; p = 0.02), and hypergammaglobulinemia (35% vs. 64%; p = 0.023). In multivariate analysis, sensorimotor neuropathy was associated with the presence of B-NHL (odds ratio [OR], 39.0; p < 0.001), whereas nonataxic sensory neuropathy was associated with the presence of CNS involvement (OR, 17.0; p = 0.025) and ANA (OR, 0.07; p < 0.001). In conclusion, we found that up to 25% of pSS patients presented with PN, predominantly sensory neuropathy. Distinctive immunologic profiles were found according to the type of SS-associated neuropathy: nonataxic sensory neuropathy was marked by a low prevalence of B-cell activation markers, and sensorimotor neuropathy was marked by a high prevalence of B-cell monoclonal proliferation markers.