Natural killer (NK) cells are ideal candidates for immunotherapy because they can target many different cancers. It’s becoming increasingly clear that subsets of NK cells exist that differ in their capacity to lyse targets, produce cytokines, proliferate and survive. We have characterised NK cell subsets that expand following cytomegalovirus (CMV) reactivation in patients receiving umbilical cord blood (UCB) transplants for the treatment of haematological cancers. These NK cells have enhanced functional potential and survival capacity. Considering CMV is associated with reduced risk of leukaemic relapse in recipients of haematopoietic stem cell transplantation, we sought to identify additional changes occurring in NK cells from patients receiving UCB transplants. It is thought that all NK cells express the signalling adaptor molecules Eat-2, FcεRIγ and the tyrosine kinase Syk. In a cohort of 84 UCB transplant recipients we found that NK cells lacking Eat-2, FcεRIγ or Syk were significantly increased in patients who reactivated CMV compared with those that did not. Moreover, these cells preferentially expanded during the first year after transplant. While a higher proportion of these cells co-expressed NKG2C, this was not significant, indicating the expansion of a novel population of NK cells that were distinct from the expanding NKG2C+ NK cells. NK cells lacking Eat-2 or FcεRIγ produced significantly more IFN and TNFα when cross-linked with CD16 or when stimulated with PMA compared with conventional NK cells. Furthermore NK cells that co-expressed CD57 were even more potent at producing cytokines. Collectively, these findings suggest that CMV reactivation post-transplant expands multiple subsets of NK cells all with enhanced capacity to mediate antibody dependent responses and eliminate transformed cells. These findings provide the basis for developing future NK cell immunotherapy protocols for use in the clinic to treat patients with leukaemia.