As the COVID-19 pandemic poses severe threats to human life around the globe, effective risk messages are needed to warn the public and encourage recommended actions for avoiding infection, especially as steps are taken to ease physical restrictions and restart economies. The present study examines the effects of agency assignment and reference point on perceptions of SARS-CoV-2 threat and assesses key message responses, including psychological reactance, source derogation, counterarguing, and behavioral intentions. Participants (N = 207) were randomly assigned to one of four conditions crossing agency assignment (SARS-CoV-2/human) and reference point (self/self-other). Results show, relative to human agency, SARS-CoV-2 agency assignment generated significantly more psychological reactance in the form of greater perceptions of freedom threat, anger, and negative cognitions, as well as more source derogation and counterarguing. No significant effects were found for reference point, and the interaction between agency assignment and reference point was not significant. The study findings, limitations, and implications are discussed.