Background: The risk of cytokine release syndrome (CRS) in patients with infections prior to chimeric antigen receptor T‐cell (CAR T‐cell) therapy represents an important and underreported event. Patients with active infections needing prompt CAR T‐cell therapy to treat aggressive hematologic malignancies remain a clinical challenge.Case Report: This case describes the clinical course of a 35‐year‐old male patient with relapsed/refractory T‐cell/histiocyte‐rich large B‐cell lymphoma who received axicabtagene ciloleucel. The patient developed ASTCT Grade II CRS on day +5, necessitating hospital admission and intravenous antibiotics, dexamethasone and tocilizumab. The patient was found to have a Pneumocystis jirovecii pneumonia (PJP) infection 3 days prior to CAR T‐cell infusion and cytomegalovirus (CMV) viremia 3 days after CAR T‐cell infusion. He received TMP‐SMX for 21 days to treat PJP and valganciclovir to treat CMV viremia. PET/CT on day +26 demonstrated near resolution of pulmonary nodules and significant partial response of disease according to Deauville criteria.Conclusion: This case highlights the risk of CRS in immunocompromised patients with infections, and presents a unique case of CRS associated with PJP and CMV infections. Although the patient’s clinical course was fraught with complications, he achieved a significant partial response to CAR T‐cell therapy with the help of a multidisciplinary medical team.