Abstract Background Rituximab is a monoclonal antibody that increases the disease-free and overall survival of patients with non-Hodgkin lymphoma (NHL) CD20+. The objective of this study is to describe the prevalence and spectrum of infections in patients with NHL receiving rituximab-containing chemotherapy and the impact on survival. Materials and Methods From January 2011 to December 2012, all patients diagnosed with NHL who received at least one dose of rituximab were included. Results During the study period, 265 patients received rituximab; 108 (40.8%) males; the mean age was 60 ± 15 years. There were 177 infections in 85 patients, being the most common febrile neutropenia (n = 38; 21.5%) and mucosal barrier injury-related infections (n = 28; 15.8%). In 88 events (49%), there was a microbiologic diagnosis, being bacterial infection the most frequent (39.6%), but tuberculosis (TB) was developed in 4 cases (1.5%; incidence rate 721/100,000 person-year). During follow-up, 71 patients died (27%); in 35 cases, it was related to infection. There were no differences in follow-up between those who died due to infection versus those who died from another cause (p = 0.188). Multivariate analysis for mortality showed that age >60 years, failure to achieve a complete response, and development of an infectious complication increased the risk of death. Conclusions It is important to perform a screening test for TB in all patients who will receive rituximab and maintain a constant monitoring to detect an infectious process and begin treatment as soon as possible.