Epizootic hemorrhagic disease virus (EHDV) causes severe disease in ruminants. We assessed the pathogenicity of the Chinese EHDV-7 isolate YN09 in mice lacking the type I interferon receptor and in sheep. In mice, YN09 infection resulted in 100% mortality, with histopathological lesions, viral replication, and immunoreactivity in multiple organs. In sheep, infection with this virus resulted in transient RNAemia and low-level production of neutralizing antibodies, but no clinical signs or viremia were observed. These findings contrast YN09's high murine virulence with sheep resistance, suggesting that sheep play a negligible role in EHDV-7 transmission in China. Further studies of other natural hosts are needed in order to understand the ecology of this EHDV-7 strain.