Patients undergoing allogeneic cord blood transplantation (CBT) benefit from a low risk of graft-versus-host disease (GVHD), but there are still concerns that they be able to recover an effective immune capacity early after transplantation. We investigated the ability to develop in vitro T-lymphocyte-mediated immune response toward human cytomegalovirus and Candida albicans antigens, early and late after transplantation, in children given cord blood transplants from either an HLA-identical sibling or an unrelated donor. Proliferative capacity and frequency of antigen-specific T cells were evaluated; antigen-specific CD4(+) T-cell clones were also generated and characterized for T-cell receptor repertoire diversity, cytokine phenotype, and their origin (either from donor or patient). We found that the majority of recipients can develop a specific response to viral or fungal antigens already early after transplantation. Antigen-specific T-cell clones of both donor and recipient origin contributed to the reconstitution of immune response. Antigen-specific T lymphocytes of recipient origin were detected in patients receiving a transplant from a relative, after a chemotherapy-based conditioning regimen, and who did not have GVHD. Our results document, at a clonal level, that after CBT recovery of either polyclonal or pauciclonal T-cell response toward widespread pathogens is prompt, with some patients benefiting from a contribution of recipient-derived cells.