ABSTRACT Background: Healthcare workers (HCWs) across the globe have reported symptoms of Post-Traumatic Stress Disorder (PTSD) during the COVID-19 pandemic. Moral Injury (MI) has been associated with PTSD in military populations, but is not well studied in healthcare contexts. Moral Distress (MD), a related concept, may enhance understandings of MI and its relation to PTSD among HCWs. This study examined the independent and combined impact of MI and MD on PTSD symptoms in Canadian HCWs during the pandemic. Methods: HCWs participated in an online survey between February and December 2021, with questions regarding sociodemographics, mental health and trauma history (e.g. MI, MD, PTSD, dissociation, depression, anxiety, stress, childhood adversity). Structural equation modelling was used to analyze the independent and combined impact of MI and MD on PTSD symptoms (including dissociation) among the sample when controlling for sex, age, depression, anxiety, stress, and childhood adversity. Results: A structural equation model independently regressing both MI and MD onto PTSD accounted for 74.4% of the variance in PTSD symptoms. Here, MI was strongly and significantly associated with PTSD symptoms (β = .412, p < .0001) to a higher degree than MD (β = .187, p < .0001), after controlling for age, sex, depression, anxiety, stress and childhood adversity. A model regressing a combined MD and MI construct onto PTSD predicted approximately 87% of the variance in PTSD symptoms (r 2 = .87, p < .0001), with MD/MI strongly and significantly associated with PTSD (β = .813, p < .0001), after controlling for age, sex, depression, anxiety, stress, and childhood adversity. Conclusion: Our results support a relation between MI and PTSD among HCWs and suggest that a combined MD and MI construct is most strongly associated with PTSD symptoms. Further research is needed better understand the mechanisms through which MD/MI are associated with PTSD.