The mission of RESPOND is 1) to identify critical resilience factors and specific vulnerable groups at risk of immediate and long-term adverse mental health impact of the COVID-19 pandemic; 2) To improve the resilience, wellbeing and mental health of frontline health and care workers and other vulnerable groups by implementing scalable World Health Organization (WHO) programmes, and 3) to steer future policy decisions by understanding and disentangling the effects of the COVID-19 pandemic and different public health containment and subsequently relaxation strategies on mental health and wellbeing in vulnerable groups across Europe’s different health systems. RESPOND is centred around core questions regarding the short and long-term impacts of the pandemic on mental health and health inequalities on vulnerable groups within the general population, including frontline workers. In the first immediate delivery phase, an impressive set of existing longitudinal datasets are examined for resilience factors and risk factors. Furthermore, the responsiveness of health systems and identification of best practice responses that protect resilience, mental health and wellbeing are assessed in eight EU countries. The long-terms effects are determined of the pandemic and the control measures on demand for (mental) health services in health registers in Sweden, Lombardy and Barcelona and the scalable WHO SH+/PM+ stepped care programmes adapted for COVID-19 will be implemented and evaluated both in frontline workers and vulnerable groups. RESPOND provides policy recommendations within 3 months on vulnerability factors for developing poor mental health resulting from current containment and mitigation measures. Further lessons learnt and evidence-based policy recommendations will be made available during the project’s lifetime through Policy Briefs in month 6, 12, 18, 24 and 36 for immediate consideration and use by all EU member states.