Objective: Studies have shown that school leaders’ health literacy is key to supporting health development in school. During the COVID-19 pandemic, the importance of school leaders’ health literacy became evident, as school leadership was characterised with uncertainty and demanded high levels of alertness to the need to implement rapidly changing health-related measures at short notice. This study sought to explore school leaders’ health literacy, mental health and work-related characteristics in Danish public primary and lower secondary schools during the pandemic. Methods: Selecting schools from the national Danish register of institutions a sample of 220 complete responses was achieved in a cross-sectional survey. School leaders or a member of the school management team completed a self-administered version of the COVID-HL: School Principals Survey, which assessed health literacy, three domains of mental health, sense of coherence and workload. Data were analysed using chi-square tests and logistic regression. Results: The majority of school leaders (71.4%) demonstrated a sufficient level of health literacy. However, there was a significant difference in workload increase between those with sufficient (66.0%) and insufficient (81.6%) health literacy. A high general workload was associated with lower well-being, while an increase in workload during the COVID-19 pandemic was linked to psychosomatic complaints. Sense of coherence explained variations in well-being, emotional exhaustion and psychosomatic complaints. Conclusion: This study highlights the importance of enhancing the health literacy of Danish school leaders, enabling them to deal effectively with complex health-related information and make informed decisions during health crises. Strengthening health literacy is crucial to promoting overall health and well-being in schools under normal circumstances, as well as navigating health crises.