IntroductionThe unprecedented COVID-19 pandemic has exposed healthcare professionals (HCPs) to exceptional situations that can lead to increased anxiety (ie, infection anxiety and perceived vulnerability), traumatic stress and depression. We will investigate the development of these psychological disturbances in HCPs at the treatment front line and second line during the COVID-19 pandemic over a 12-month period in different countries. Additionally, we will explore whether personal resilience factors and a work-related sense of coherence influence the development of mental health problems in HCPs.Methods and analysisWe plan to carry out a sequential qualitative–quantitative mixed-methods design study. The quantitative phase consists of a longitudinal online survey based on six validated questionnaires, to be completed at three points in time. A qualitative analysis will follow at the end of the pandemic to comprise at least nine semistructured interviews. The a priori sample size for the survey will be a minimum of 160 participants, which we will extend to 400, to compensate for dropout. Recruitment into the study will be through personal invitations and the ‘snowballing’ sampling technique. Hierarchical linear regression combined with qualitative data analysis, will facilitate greater understanding of any associations between resilience and mental health issues in HCPs during pandemics.Ethics and disseminationThe study participants will provide electronic informed consent. All recorded data will be stored on a secured research server at the study site, which will only be accessible to the investigators. The Bern Cantonal Ethics Committee has waiv ed the need for ethical approval (Req-2020–00355, 1 April 2020). There are no ethical, legal or security issues regarding the data collection, processing, storage and dissemination in this project.Trial registration numberISRCTN13694948.