Borrelia burgdorferiis a human pathogen vectored byIxodesticks and maintained in nature by a suite of competent vertebrate reservoirs. White-tailed deer (WTD) are considered to be noncompetent reservoirs forB. burgdorferi. Sera from other deer species have been found to be borreliacidal, and similar mechanisms could explain the lack of reservoir competence of WTD. Therefore, we determined whether WTD serum can killB. burgdorferi.Using anin vitroserum sensitivity assay and subculturing of spirochetes, we demonstrated that WTD serum effectively killsB. burgdorferi. The borreliacidal activity of WTD serum likely contributes to the inability of WTD to efficiently harbor and transmitB. burgdorferi.