Mannose-binding lectin (MBL) deficiency has been suggested as a risk factor for certain viral infections. However, there is no data about the possible association between MBL deficiency and cytomegalovirus (CMV) infection, especially after organ transplantation. We measured plasma MBL levels in 16 kidney transplant recipients with high-risk CMV serostatus (donor-positive/recipient-negative). MBL deficiency was diagnosed if MBL levels were <500 ng/mL. Of these 16 patients, seven developed CMV disease, four developed asymptomatic CMV infection, and in five patients CMV replication was not detected. Overall, 9 of 16 patients (56%) had MBL deficiency: five of seven (71%) patients with CMV disease, four of four (100%) patients with asymptomatic CMV infection, and zero of five (0%) patients without CMV infection (P=0.005; CMV infection/disease versus no infection). MBL deficiency may be a significant risk factor for the development of CMV infection in kidney transplant recipients, suggesting a role for innate immunity in the control of CMV infection after organ transplantation.