Cytokines play important roles in the pathogenesis of lymphomas. This study aimed to determine the relationship(s) between serum levels of interleukin (IL)‐6, IL‐8 and IL‐10, measured by enzyme‐immunoassay, and the clinical characteristics and outcomes in 46 untreated patients with diffuse large B‐cell lymphoma (DLBCL). Serum IL‐6, IL‐8 and IL‐10 levels were higher in DLBCL patients than in control subjects. Elevated levels of IL‐6, IL‐8 and IL‐10 correlated with more adverse disease features. Consequently, patients with elevated IL‐6, IL‐8 and IL‐10 levels prior to treatment had a lower response to therapy. Furthermore, those with elevated IL‐6 and IL‐10 levels had poor median, 3‐year and 5‐year survival, while elevated serum IL‐8 level did not correlate with overall survival. Worse survival was also confirmed in patients with combined elevated pretreatment serum levels of IL‐6, IL‐8 and IL‐10 (none, one, two or three elevated). Multivariate analysis identified elevated values of IL‐6 and IL‐10 and response to therapy as significant predictors for overall survival. Serum levels of IL‐6, IL‐8 and IL‐10 before treatment of patients with newly diagnosed DLBCL may give some insight into the possible prognosis and thus facilitate the decisions regarding therapeutic approaches for individual patients.