Persistent viral infections often overburden the immune system and are a major cause of disease in humans. During many persistent infections, anti-viral T cells are maintained in a state of immune exhaustion characterized by diminished effector and helper functions. In mammalian systems an extensive immune regulatory network exists to limit unwanted, potentially fatal immunopathology by inducing T cell exhaustion. However, this regulatory network at times overprotects the host and fosters viral persistence by severely dampening adaptive immune responsiveness. Importantly, recent studies have shown that T cell exhaustion is mediated in part by host immunoregulatory pathways (e.g. PD-1, IL-10) and that therapeutic blockade of these pathways either before or during persistent infection can promote viral clearance. Transforming growth factor beta (TGF-β) is another immunosuppressive cytokine known to impede both self- and tumor-specific T cells, but its role in regulating anti-viral immunity is not entirely understood. In this study we inhibited TGF-β with three potent antagonists to determine whether neutralization of this regulatory molecule is a viable approach to control a persistent viral infection. Our results revealed that these inhibitors modestly elevate the number of anti-viral T cells following infection with a persistent variant of lymphocytic choriomeningitis virus (LCMV), but have no impact on viral clearance. These data suggest that therapeutic neutralization of TGF-β is not an efficacious means to promote clearance of a persistent viral infection