The aim was to investigate circulating levels of interelukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, chemokine (C-X-C motif) ligand (CXCL)10, CXCL11 and chemokine (C-C motif) ligand (CCL)2 in "mixed cryoglobulinemia and hepatitis C" (MC + HCV). Serum levels of CXCL11, IL-1β, TNF-α, IL-6, and CCL2 were evaluated in 52 MC + HCV vs 52 sex- and age-matched controls to correlate them to the clinical features of mixed cryoglobulinemia. CXCL11 was significantly higher in MC + HCV than in controls (264 ± 279 vs 70 ± 16 pg/mL, respectively; P = 0.0002; univariate analysis of variance (ANOVA)), in particular in 23 MC + HCV with active vasculitis vs those without (293 ± 221 vs 168 ± 57 pg/mL, respectively; P < 0.001; ANOVA). Significantly high IL-1β, IL-6, TNF-α, CXCL10, and CCL2 in MC + HCV vs healthy controls were confirmed. In a multiple linear regression model (CXCL11 or CCL2, vs age, alanine aminotransferase, IL-1β, IL-6, TNF-α, and CXCL10), CXCL11 was significantly associated with high CXCL10 (P < 0.001), while CCL2 with high IL-6 (P < 0.001). This study demonstrates in MC + HCV high serum levels of (a) T-helper 1 chemokines, CXCL11 and CXCL10 (related to each other) and (b) proinflammatory cytokines IL-6 and CCL2 (related to each other).