In the wake of COVID-19, unemployment and its potential deleterious consequences have attracted renewed interest. We examined (1) the association between unemployment, occurring upon the coronavirus outbreak, and psychological distress among Israeli young people (20–35-years-old); (2) the associations between various psychological resources/risk factors and psychological distress; and (3) whether these resources and risk factors were moderators in the unemployment-psychological distress link. A real-time survey based on snowball sampling was conducted during the month of April 2020 (N = 390). We employed hierarchical linear models to explore associations between unemployment, psychological resources, risk factors, and psychological distress. Unemployment was independently associated with greater psychological distress. Perceived trust, optimism, and sense of mastery decreased psychological distress, whereas financial strain and loneliness during the crisis increased this distress. The effect of unemployment on psychological distress did not depend on participants’ resource and risk factor levels. Policymakers must develop and extend health initiatives aimed at alleviating the mental health consequences of COVID-19-related unemployment and promote labor market interventions to help young job seekers integrate into employment. These measures, which are in line with the UN sustainable development goals, should be seen as an important route to promote public health.