CD19‐chimeric antigen receptor T‐cell (CAR T‐cell) therapy has improved the outcomes of relapsed/refractory large B cell lymphoma significantly. However, about 50% of patients relapsed post‐CAR‐T therapy. Late relapse composed of 1/3 to 1/2 of CAR‐T cell therapy failure, with no previous reports of isolated relapse in immune‐privileged sites. Here, we report the first case series of late‐onset post CAR‐T cell therapy isolated central nervous system (CNS) relapses, in systemic relapsed/refractory large B cell lymphoma patients. With these cases, we suggest that additional CNS prophylaxis should be administrated for primary refractory patients on CAR‐T cell therapy with previous neurological involvements, multiple extra‐nodular lesions, and high CNS‐IPI score pre‐CAR, as well as early disappearance of circulating CAR‐T cells post infusion.