Introduction: The COVID-19 pandemic generated a significant burden on the German health care system, affecting the mental health of health care workers (HCW) in particular. Resilience may serve as an essential protective factor for individuals' well-being. Objective: Our objective was to identify demographic and work-related correlates of individual resilience and to investigate the association between pandemic-related stress, resilience and mental health using different resilience models. Methods: Our sample comprised 1034 German HCW in different medical professions who completed an online survey from 20 April to 1 July 2020. Resilience was assessed using the Resilience Scale-5 (RS-5). The pandemic-related self-reported stress burden was captured by a single item, while depression and anxiety symptoms were measured with the PHQ-2 and GAD-2, respectively. Additionally, various sociodemographic and work-related factors were assessed. Results: Overall, we found high levels of resilience in the sample compared to a German sample before the pandemic, which were significantly associated only with the older age of participants and having children in both univariate and multivariate analyses. Regarding mechanisms of resilience, moderation analysis revealed that low individual resilience and high pandemic-related stress burden independently contributed to both anxiety and depression symptoms while resilience additionally moderated the relationship between stress burden and anxiety symptoms. The link between self-reported stress burden and mental health symptoms was also partially mediated by individual resilience. Conclusion: Taken together, the findings based on the present sample during the COVID-19 pandemic suggest that resilience plays a central role in the mental health of healthcare workers and that resilience-building interventions should be expanded, especially with a focus on younger employees.