Health risk exposure during the global COVID-19 pandemic has required people to adopt self-isolation. Public authorities have therefore had the difficult task of sustaining such protective but stressful behaviour. Evidence shows that besides egoistic drives, the motivation for self-isolation behaviour could be altruistic. However, the type and role of prosocial motivation in the current pandemic is underestimated and its interaction with risk exposure and psychological distress is largely unknown. Here we show that affective empathy for the most vulnerable predicts acceptance of lockdown measures. In two retrospective studies, one with a general population and one with COVID-19 positive patients, we found that (1) along with health risk exposure, affective empathy is a predictor of acceptance of lockdown measures (2) social covariates and psychological distress have no significant impact. Our results support the need to focus on altruistic behaviours while informing the public instead of on fear-inducing messages.