Background Healthcare workers frequently face ethically demanding situations in their work, potentially leading to stress of conscience. Long-term work intensification (more and more effort demanded year after year), organizational change and COVID-19 may be risk factors concerning stress of conscience. Aims The main aim was to investigate the relationship between long-term work intensification and stress of conscience among the personnel in a healthcare organization. Organizational change management was considered a mediator and COVID-19-related work stress a moderator in the association between (...) work intensification and stress of conscience. Research design, participants and context A total of 211 healthcare district employees participated in a longitudinal survey using questionnaires collected in 2019 (major organizational change in the planning stage) and 2021 (organizational change completed). Ethical considerations The study was implemented according to the guidelines of the Finnish National Board on Research Integrity. The Finnish instructions were that no review by an ethics committee was necessary because participation was voluntary, informed consent was requested, participants were assured that they were free to withdraw from the longitudinal study at any time and no health data were collected. Findings Long-term work intensification was associated with more severe stress of conscience. Long-term work intensification was partially mediated through change management to stress of conscience. High COVID-19 stress strengthened the association between long-term work intensification and stress of conscience. Conclusions Long-term work intensification must be addressed to reduce stress of conscience in healthcare, otherwise the healthcare system will be vulnerable to changes and crisis. Extra resources for personnel and management should be allocated because of work intensification during organizational change and health crises like the COVID-19 pandemic to alleviate stress of conscience. (shrink)