Background and objectiveTo analyse the association between interferon-1α (INF1α), interleukin-10 (IL-10) and BLyS concentrations and clinical activity in systemic lupus erythematosus (SLE). Patients and methodsA cross-sectional, observational study of 142 SLE patients and 34 healthy controls was performed, through a complete blood and urine test and review of their medical history. Serum concentration of INF1α, IL-10 and BLyS was determined by colorimetric methods. A biostatistical analysis was performed with R (3.3.2). Results69% of our SLE patients showed at least one cytokine increased. INF1α, IL-10 and BLyS are higher in SLE patients than in healthy controls (p<0.001, p=0.005 and p=.043, respectively), being INF1α the most frequent. Patients were categorised according to low or high concentrations of the three cytokines. We found a significant association between increased IL-10/INF1α concentrations and a higher clinical activity measured by SELENA-SLEDAI (p<0.0001) and, to a lesser extent, an association with increased INF1α/IL-10/BLyS concentrations. Elevated levels of IL-10/INF1α and INF1α/IL-10/BLyS related to increased C3-C4 consumption (p<0.001 and p=0.001, respectively) and anti-dsDNA titres (p=0.001 and p=0.002, respectively). Elevated INF1α/BLyS related to higher anti-dsDNA titres (p=0.004) and ENA positivity (p<0.001). Increased levels of INF1α/IL-10/BLyS related to positivity of ANAs (p<0.001) and APL (p=0.004). ConclusionsINF1α, IL-10 and BLyS are higher in SLE patients than in healthy controls. Increased IL-10 levels, regardless of whether or not there were also increased levels of BLyS and/or INF1α, was the cytokine that best fit with clinical activity in SLE measured with classic methods.