The emergence of rituximab has changed the clinical outcome of patients with B-cell lymphoma, which necessitates reassessment of previously determined prognostic factors. Thus, we evaluated the prognostic significance of serum soluble interleukin-2 receptor (sIL2R) levels in patients with diffuse large B cell lymphoma (DLBCL), treated with CHOP (n = 108) or RCHOP (n = 94). Serum sIL2R level ranged from 316 to 23 800 U/mL (median 1064 U/mL) and levels were generally higher in higher IPI risk group. Multivariate analyses revealed that sIL2R > or =1000 U/mL was associated with shorter progression free survival [hazard ratio (HR) = 2.52, p = 0.011] and overall survival (HR = 2.34, p = 0.037) independent of IPI risk group or rituximab use. Further subgroup analyses revealed that the impact of sIL2R was most apparent in patients with IPI low risk, both in CHOP alone and RCHOP group. Our study confirmed the prognostic value of sIL2R in patients with DLBCL with low International Prognostic Index (IPI) risk, also in the era of rituximab.