Background <p>Moral distress is recognized as an important psychological risk factor in nursing practice, potentially negatively impacting nurses’ mental health and ethical nursing decision-making. However, little is known about ICU nurses’ moral resilience and the underlying mechanisms of moral distress.</p> Objective <p>To explore the mediating effect of ICU nurses’ moral disengagement between moral resilience and moral distress, and to provide a basis for nursing managers to take targeted measures to reduce the level of ICU nurses’ moral distress, to promote the quality of nursing services and to improve nurses’ ethical decision-making ability.</p> Methods <p>A convenience sampling method was used to select 334 adult ICU nurses from several hospitals in Henan and Hubei Provinces, China, using a general information questionnaire, a moral resilience scale, a moral disengagement scale, and a moral distress scale. Structural equation modeling was used to test the mediating effect of moral disengagement between moral resilience and moral distress.</p> Results <p>305 questionnaires were finally included. Moral resilience scores were 43.40 ± 6.64 Moral shirking scores were 91.40 ± 34.37 Moral distress scores were 119.44 ± 65.87 Moral resilience was negatively correlated with moral shirking and moral distress, respectively (<i>p</i> &lt; 0.05), and moral shirking and moral distress were positively correlated (<i>p</i> &lt; 0.05). Moral disengagement mediated the relationship between moral resilience and moral distress, with the mediating effect accounting for 45.39% of the total effect.</p> Conclusion <p>Nursing managers should pay attention to the role of ICU nurses’ moral resilience and reduce the reliance on moral disengagement mechanisms, thereby reducing moral distress and facilitating nurses’ ethical decision-making.</p> Clinical trial number <p>Not applicable.</p>