In this study, the objective is to understand the causal factors that influence the mental well-being of healthcare workers during the COVID-19 pandemic, using Karasek’s Job Demand Control Social Model (JDCS) as the research framework. For this purpose the database Eurofound’s Living Working and COVID-19 survey is used; it was carried out using sampling design techniques in all 27 countries of the European Union. A sample of 4626 employees in the health sector is used, and structural equation models are specified to analyze causality. The analysis revealed significant associations between several factors: physical and mental work demands (p < 0.001), availability of personal protective equipment (p = 0.035), support from supervisors (p < 0.001), support from peers (p < 0.001), and age (p < 0.007). These findings, offering valuable insights into understanding and improving the management of health institutions, can serve as a foundation for developing strategies to support and enhance the mental health of healthcare professionals. Ultimately, this benefits both the workforce and the quality of healthcare services provided, particularly in preparing for potential future crises.