To save lives and slow the spread of COVID-19 Greece imposed a country-wide, 6-week lockdown and a stay-at-home order at an early stage. This study examines the effect of quarantine on young adults by assessing depression, anxiety, stress and the experience of positive and negative affect. The role of potential risk factors such as disruption of normal life, perceived threat of the disease, acquaintance with someone infected and gender; and protective factors, such as adherence to a daily routine and altruism was evaluated. An online questionnaire entailing demographics, the Depression, Anxiety and Stress Scales (DASS-21), the Positive and Negative Affect Schedule (PANAS), measures of life disruption, perceived threat and adherence to a daily routine and an altruism scale was completed by 1018 undergraduates. Increased levels of depression, anxiety, stress and negative affect were found. Life disruption and perceived threat of the disease were risk factors in all psychological distress measures, while a stable, satisfying daily routine and altruism mitigated the negative consequences. Gender was a moderator. Acknowledging the psychological effect of quarantine on young adults should be the starting point for interventions. Helping people build a new routine and assign an altruistic meaning to the confinement can protect psychological health.