Autoimmune diseases (ADs) increase the risk of non-Hodgkin’s lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan–Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple (≥3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P<0.001) and OS (68.5% vs. 85.8%, P=0.001) than those without multiple abnormal immunologic markers. Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P=0.008, P<0.001) and OS (P=0.003, P<0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P=0.001) and age>60 years for OS (P=0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.