Although the COVID-19 pandemic has officially ended, outbreaks still occur, especially in immunocompromised patients, including those undergoing chimeric antigen receptor T-cell (CAR T-cell) therapy, who have weakened immune systems due to prior treatments or CAR T-related effects such as severe and prolonged neutropenia, lymphopenia and hypogammaglobulinemia. This retrospective study analyzed relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving CAR T-cell therapy, assessing the impact of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on overall survival (OS), progression-free survival (PFS), and delays in leukapheresis and CAR T-cell infusion. Among 89 infused patients, 37 (41.6%) developed COVID-19. Compared to the COVID + cohort, COVID- patients had worse prognostic scores and higher LDH and ferritin levels before infusion. SARS-CoV-2 infection delayed leukapheresis (14-35 days) and CAR T-cell infusion (20-65 days). The best overall response rate (BRR) in the CAR T-cell population was 77.5% (69/89 patients), with a complete response (CR) rate of 67%. The BRR was 100% in COVID + patients vs. 61.5% in COVID-. Median PFS was 5.47 months in the COVID- cohort and not reached in the COVID + cohort (p = 0.007). Median OS was 19 months in COVID- patients and not reached in COVID+ (p < 0.0001). No significant survival differences were found between COVID + and COVID - patients. Improved outcomes likely resulted from widespread vaccination, prophylaxis, early antiviral treatments, and the emergence of less virulent SARS-CoV-2 variants, reducing disease severity and mortality, allowing for better management of these patients.