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Objectives: Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T‐cell therapy in patients with large B‐cell lymphoma (LBCL). Methods: We retrospectively reviewed clinical records of LBCL patients treated with CD19‐targeted CAR T‐cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T‐cell infusion until disease progression, death or last follow‐up. Results: Overall, 137 patients were included. Thirty six percent had received ≥3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto‐HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR‐T treatment. Infection‐related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto‐HCT, ≥3 lines of treatment and pre‐lymphodepletion neutropenia. Conclusions: Infections after CAR T‐cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach. [ABSTRACT FROM AUTHOR]