There should be a heightened index of suspicion for Parvovirus B19 (PVB19)-related anemia in organ transplant recipients. Thus far, there is no consensus or recommendation for clinical routine monitoring methods of PVB19 recipients to allow tailoring of immunosuppression.We conducted a retrospective study to evaluate the utility of the function (represented by the abilities to secrete IFN-γ) and numbers of lymphocyte subsets in monitoring PVB19 infections in renal recipients posttransplant. The enrolled 109 patients were split into 2 groups according to whether the recipients had an occurrence of PVB19 infection: 37 (33.94%) recipients developed PVB19 infection and 72 (66.06%) immune-stable recipients.The PVB19 infected group had significantly lower absolute counts and functions of different lymphocyte subsets compared with immune-stable recipients. We showed that the frequencies of IFN-γ + CD4 + T cells, IFN-γ + CD8 + T cells, and IFN-γ + NK cells increased markedly after treatment when compared to the occurrence in patients with timepoint before therapy, especially the percentages of IFN-γ + CD4 + T cells were significantly higher. Receiver operating characteristic (ROC) analysis showed that the optimal infection indicator was IFN-γ + NK cells frequency, with an auROC curve of 0.925. Concomitantly, Cox regression analysis indicated that the post-therapy increasing level of IFN-γ secreting function was significantly predictive of recurrent infections (P < 0.001).We recommend prospective risk stratification for the high-risk population at risk of early-onset PVB19 infection and its recurrence involves screening strategies of immune-based surveillance with the sensitive IFN-γ + secreting monitoring for antiviral prophylaxis and preemptive therapy goal. Clinical Trial Notation: clinical trial registration number: chiCTR-ROC-17010756.Copyright © 2021. Published by Elsevier B.V.