Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that can cause severe disease and mortality in immunocompromised individuals, including kidney transplant recipients (KTRs). KTRs most at risk from HCMV infection are seronegative recipients (R-) who receive a kidney from an HCMV-infected donor (D+). Some D+R- patients develop HCMV viraemia while others do not, and the immunological and metabolic factors that determine this are poorly understood. We performed single-cell RNA sequencing of peripheral blood mononuclear cells from D+R- patients following transplantation, and compared responses in individuals that subsequently developed HCMV viraemia or not. D+R- patients that avoided viraemia displayed immunological differences (e.g., proliferation, cytokines, transcription factors) in NK cells as compared to those that developed viraemia, implying that immunological responses contribute to lack of viraemia in some patients. Furthermore, single-cell flux estimation analysis that characterises cellular metabolism revealed impaired NK cell metabolism in individuals that subsequently developed viraemia. Based on these results, flow cytometric panels were applied to D+R- KTR NK cells, to study key metabolic pathways across a HCMV viraemia timecourse. Additionally, viral dissemination assays of healthy donor PBMCs with metabolic inhibitors were used to explore metabolic impacts on NK cell control of HCMV.  Inhibition of specific metabolic pathways, indicated in our scRNA seq data, led to impaired viral control. Take together, these data suggest that HCMV viraemia occurrence in KTRs may be pre-determined by definable immunological and metabolic parameters, that could help predict HCMV viraemia occurrence and uncover intervention strategies to prevent viraemia in immunocompromised patients.