The aim of the study was to confirm whether plasma levels of interleukin-10 (IL-10) correlate with the prognosis in diffuse, large B-cell lymphoma (DLBCL) patients. Plasma IL-10 levels were determined at the time of diagnosis in a group of 157 consecutively treated, DLBCL patients. Of those, 122 patients (78%) had IL-10 plasma levels below the detection limit (< 5 pg/mL) and 35 (22%) above this value. The median value for patients with detectable IL-10 levels was 35 pg/mL (range, 5 to 2480 pg/mL). Detectable plasma IL-10 levels were significantly associated with age> 60 years, ECOG performance status≥ 2, Ann Arbor advanced disease stage, bulky tumor mass, elevated serum levels of LDH and β2-microglobulin, presence of anemia and low serum albumin levels as well as the presence of B symptoms. The patients with detectable IL-10 levels had lower probability of CR achievement (OR= 0.23, 95% CI 0.1-0.5, p= 0.0003). In addition, detectable IL-10 levels were significantly associated with shorter PFS (OR= 2.5, 95% CI 1.5-4.4, p= 0.001) and OS (OR= 3.0, 95% CI 1.7-5.2, p= 0.0001). In conclusion, we confirmed in this large group of DLBCL patients that elevated plasma IL-10 levels correlated with adverse disease features and poor prognosis. The plasma concentration of IL-10 may be a useful marker for evaluation of disease activity.