*Purpose: Cytomegalovirus (CMV) infection is associated with graft rejection in renal transplantation. Memory-like NK cells expressing NKG2C and lacking FcεRIγ are established during CMV infection.

*Methods: Here, we interrogated the in vivo kinetics of lymphocytes in CMV-infected renal transplant patients using longitudinal samples, compared with non-viremic (NV) patients. Recipient CMV seropositive (R+) patients had pre-existing memory-like NK cells (NKG2C⁺CD57⁺FcεRIγ^–) at baseline, which decreased in the periphery immediately after transplantation in both viremic and NV patients.

*Results: We identified a novel subset of pre-memory-like NK cells (NKG2C⁺CD57⁺FcεRIγ^low-dim) that increased during viremia in R+ viremic patients. These cells showed a higher cytotoxic profile than pre-existing memory-like NK cells with transient upregulation of FcεRIγ and Ki67 expression at the acute phase, with the subsequent accumulation of new memory-like NK cells at later phases of viremia. Furthermore, cytotoxic NKG2C⁺CD8⁺ T cells and cytotoxic γδ T cells significantly increased in viremic patients and these three different cytotoxic cells combinatorically responded to viremia.

*Conclusions: All viremic patients, except one, overcame viremia and didn’t experience graft rejection. These data provide new insights into in vivo dynamics and interplay of cytotoxic lymphocytes responding to CMV viremia, which are potentially linked with control of CMV viremia to prevent graft rejection.

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