The COVID-19 pandemic has affected the lives of people worldwide. Governments struggled to persuade citizens to obey ongoing lockdowns and social restrictions to fight the transmission of the virus. The purpose of this paper is to investigate the impact of prosocial behavior during COVID-19 and big-five personality traits on compliance with health-protective behavior against COVID-19. To examine possible predictors an online questionnaire was delivered to undergraduate students at a public university of Athens during the second phase of the pandemic (November 2020). A mediation analysis was performed to test the relationships among variables. The sample consisted of 239 business school students and the results revealed that two of the big-five personality traits of young adults, conscientiousness, and neuroticism, can be linked with a positive attitude to following heath precautions and recommendations while conscientiousness and agreeableness are predictors of young adults’ prosociality behavior to cope with the COVID-19 pandemic. Finally, the results indicated that there is not any effect of young adults’ personality traits on health recommendation through the mediation of prosociality. The results will contribute to the recent literature (Campos-Mercade, Meier, Schneider, & Wengström, 2021; Miles, Andiappan, Upenieks, & Orfanidis, 2021) on the factors influencing prosocial decision-making regarding the pandemic.