We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf‐1 (DKK‐1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK‐1 and increased secreted frizzled related protein‐3 levels were predictors of poor virological outcomes during follow‐up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection. An imbalanced pattern of the secreted Wnt modulators Dickkopf‐1 and secreted frizzled related protein‐3 is a predictor of poor virological outcome following treatment for cytomegalovirus disease in solid organ transplant recipients.