COVID-19 vaccine hesitancy is a new phenomenon in Syria, about which relatively little is known. We aimed to explore this, drawing from 37 semi-structured interviews with frontline health-workers and service-users across Syria's major military areas-of-control. We found COVID-19 vaccine hesitancy was common and increasing among service-users and less common, but still present, among health-workers in all areas. Interrelated reasons included pragmatic fears of novel vaccine risks, unreliable information, and conflict-related hesitancies as a form of resistance or reasserting some perceived control, particularly outside Al-Assad government-controlled areas. Vaccine hesitancy has thus become a socio-political issue, requiring macro-level responses, across Syria.