Background: Potentially morally injurious events (PMIEs) can negatively impact mental health. The COVID-19 pandemic may have placed healthcare staff at risk of moral injury. Aim: To examine the impact of PMIE on healthcare staff wellbeing. Methods: Twelve thousand nine hundred and sixty-five healthcare staff (clinical and non-clinical) were recruited from 18 NHS-England trusts into a survey of PMIE exposure and wellbeing. Results: PMIEs were significantly associated with adverse mental health symptoms across healthcare staff. Specific work factors were significantly associated with experiences of moral injury, including being redeployed, lack of PPE, and having a colleague die of COVID-19. Nurses who reported symptoms of mental disorders were more likely to report all forms of PMIEs than those without symptoms (AOR 2.7; 95% CI 2.2, 3.3). Doctors who reported symptoms were only more likely to report betrayal events, such as breach of trust by colleagues (AOR 2.7, 95% CI 1.5, 4.9). Conclusion: A considerable proportion of NHS healthcare staff in both clinical and non-clinical roles report exposure to PMIEs during the COVID-19 pandemic. Prospective research is needed to identify the direction of causation between moral injury and mental disorder as well as continuing to monitor the longer term outcomes of exposure to PMIEs.