The present study investigated the effect of interpersonal mistreatment on the perpetrators’ mental health. We proposed that the threat of COVID-19 will increase people’s mental health problems through their on-line aggression toward stigmatized groups accused of spreading the disease and that there might be potential gender differences in such effects. We tested our predictions among a sample of U.S. residents (Study 1) and a large sample of Chinese residents living out of Hubei province (Study 2) during a heightened period of concern about COVID-19, February 2020. Specifically, we measured U.S. residents’ on-line aggressive behaviors toward Chinese people (Study 1) and Chinese non-Hubei residents’ on-line aggressive behaviors toward Hubei residents (Study 2) as well as their neuroticism (Study 1) and mental health states (Study 2). In line with our predictions, both studies showed that perceived infection of COVID-19 can induce on-line aggression toward stigmatized groups, thereby increasing people’s mental health problems. Moreover, the relationship between COVID-19 vulnerability, on-line aggression, and psychosomatic symptoms was more prominent in men than in women. These results offer insights into people’s responses toward COVID-19 and add to the understanding of people’s mental and physical health during the epidemic stage of contagious diseases.