Background: Infections due to Sand-fly virus (SFV) are common in the Mediterranean region, but are rarely diagnosed in Israel. Until recently, no cases of severe neuro-invasive SFV infections were reported. In this study, we describe two cases of encephalitis associated with seroconversion to SFV acquired in Israel. We further try to postulate about the infecting strain of the SFV, its local phlebotomine vector, and the reasons for the emergence of this infection in Israel.