To identify risk factors for infection in patients with diffuse large B cell lymphoma (DLBCL) undergoing rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone (R-CHOP) treatment. All patients with DLBCL who received R-CHOP from 2004-2014 in a tertiary Australian hospital were identified and information collected from hospital admission data, laboratory results and medical record review. Infection was defined as hospitalisation with an ICD-10-AM diagnostic code for infection. Risk factors for infection and association between infection and survival were modelled using Cox proportional hazards regression. Over the 10-year period there were 325 patients; 191 (58.8%) males, median age 66 years. 206 (63.4%) patients experienced ≥1 infection. Independent predictors of infection were Charlson comorbidity index score (hazard ratio [HR] 3.60, p = 0.002), Eastern Cooperative Oncology Group (ECOG) performance status (HR 2.09 p = <0.001) and neutropenia (HR 2.46, p = <0.001). 99 (31%) patients died. Infection was an independent predictor of survival (HR 3.27, p = <0.001, as were age (HR 2.49, p = 0.001), Charlson comorbidity index (HR 4.34, p = <0.001), ECOG performance status (HR 4.33, p = 0.045) and neutropenia (HR 1.95, p = 0.047). Infections are common and infection itself is an independent predictor of survival. Patients at highest risk of infection and death are those with multiple comorbidities, poor performance status and neutropenia.