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BACKGROUND Nurses play an essential role in responding to severe viral disease which bring considerable challenges to their personal and professional well-being. This subsequently can affect the delivery of care and healthcare systems' organisational capacity to respond. Understanding nurses' experiences of these challenges will help inform healthcare policies. AIM To explore the experiences and coping strategies of nurses caring for patients during severe viral disease pandemics. DESIGN A mixed-methods systematic review informed by the Joanna Briggs Institute (JBI) methodology. METHODS A mixed-methods systematic review. Five electronic databases Medline, CINAHL, PsychInfo, ASSIA and Scopus were searched on 4th April 2021. Results were reported in accordance with PRISMA. The findings were analysed and reported in the context of the Self-Regulatory Common-Sense Model. RESULTS In total, 71 peer-review primary research articles describing nurses' experiences of caring for patients during SARS, MERS, Swine flu H1N1, Avian influenza or SARS-CoV-2 / COVID-19 published in English from 2003 to 2021 were included. We found links between nurses' perception of the health threats, their emotional reactions, and coping strategies. Perceived health threats were influenced by organisational factors including frequent changes in clinical guidelines and workplace protocols, onerous workloads and working hours, unavailability of PPE, and lack of knowledge and training in pandemic management. These impacted nurses' physical, psychological and social well-being. Nurses also reported helpful and unhelpful coping strategies to manage the health threats. CONCLUSIONS It is vital for stakeholders, policymakers, government and healthcare institutions to recognise and monitor the wider impact on healthcare workers from health emergencies. In addition, support to develop and implement effective systems and individual mechanisms to offset the anticipated impact pre and post pandemics/epidemics is needed. Our findings can inform those strategies for similar future health emergencies. RELEVANCE TO CLINICAL PRACTICE Nurses are often the first point of contact in providing direct care to patients, hence they are at high risk of being infected. The findings from this review can help managers and policymakers in developing programmes to enhance resilience in the nursing workforce. NO PATIENT OR PUBLIC CONTRIBUTION This was a literature review study.