The present cross-sectional study sought to explore the role of social support and self-esteem in alleviating the Covid-19 burdens among university students in a context characterized by political instability and conflict, such as the one of the Gaza Strip. Three hundred and fifteen university students in the Gaza Strip, 230 (73%) boys and 85 (27%) girls, compiled self-reported questionnaires (FCS-19, RSES, BSSS, ASS-14). We tested throughout stratified regression analysis the role of social support and self-esteem in influencing the relationship between fear of Covid-19 and academic stress. We expected social support and self-esteem to influence the association between the predictor (fear of Covid) and the outcome variable (academic stress). The findings showed that self-esteem was crucial in regulating the association between fear of COVID and academic stress. Social support did not. The more students perceived fear of the infection, the more they were at risk of displaying stress in their studies, while self-esteem might have regulated the sense of overload because of academic demands. The need to support students living in chronic warfare and political violence conditions, the necessity to promote social networks and potentiate their self-esteem during and beyond the pandemic outbreak emerged as urgent in the Gaza Strip.