COVID-19 represented an unprecedented challenge for health workers around the world, resulting in strong concerns about impacts on their psychological well-being. To inform on-going support and future preparedness activities, this study documented health workers' experiences, well-being and coping throughout the first wave of the pandemic, in Burkina Faso, Senegal and The Gambia. We collected data from 68 primarily clinical staff from the COVID-19 treatment, maternity and emergency departments in 13 purposely hospitals and laboratories across the three countries. Following in-depth interviews via Zoom (mid-May to September 2020), we regularly followed up via WhatsApp until the end of 2020. We used a mixed deductive and inductive coding approach and a framework matrix to organize and analyse the material. All respondents initially assessed the situation as stressful and threatening. Major emotional reactions included fear of own infection, fear of being a risk to loved ones, guilt, compassion, and anxiety regarding the future. Many suffered from feeling left alone with the emerging crisis and feeling unvalued and unappreciated, particularly by their governments and ministries of health. Conversely, health workers drew much strength from support and valuation by direct supervisors and team members and, in part, also by patients, friends and family. We observed important heterogeneity between places of work and individual backgrounds. Respondents coped with the situation in various ways, particularly with strategies to manage adverse emotions, to minimize infection risk, to fortify health and to find meaning in the adverse circumstances. Coping strategies were primarily grounded in own resources rather than institutional support. Over time, the situation normalized and fears diminished for most respondents. With a view towards emergency preparedness, our findings underline the value of participation and transparent communication, institutional support and routine training to foster health workers' psychological preparedness, coping skill set and resilience more generally.