Several studies have reported an association between CMV reactivation and a decreased incidence of relapse for AML after adult donor allogeneic hematopoietic cell transplantation (HCT). Limited data, however, are available on the impact of CMV reactivation on relapse after cord blood (CB) stem cell transplantation. The unique combination of higher incidence of CMV reactivation in the seropositive recipient and lower incidence of graft versus host disease (GvHD) in CB HCT permits a valuable design to analyze the impact of CMV reactivation. Data from 1684 patients transplanted with CB between 2003 and 2010 for AML and ALL were analyzed. The median time to CMV reactivation was 34 days (range: 2–287). CMV reactivation and positive CMV serology were associated with increased non-relapse mortality (NRM) among both AML and ALL CB recipients (reactivation, AML: relative risk (RR) 1.41 (1.07–1.85); ALL: 1.60 (1.14–2.23); Serology, AML: RR 1.39 (1.05–1.85), ALL: RR 1.61 (1.18–2.19)). For patients with ALL, but not those with AML, this yielded inferior overall survival (P< 0.005). Risk of relapse was not influenced by CMV reactivation or positive CMV serostatus for either disease.