<p>Gaining insight into the pandemic-related factors that affect nurse intentions to leave the profession is critical given the central role nurses play in the healthcare system. This study examined the relationships among patient and family mistreatment, work fatigue (mental, emotional, and physical), and intentions to leave the nursing profession due to the coronavirus disease 2019 (COVID-19) pandemic. Using a time-lagged design, we recruited 152 direct care U.S. nurses to respond to three waves of online surveys over a six-week period. Results suggest that experiences of mistreatment indirectly affect nurses’ intentions to leave the profession through experiences of mental fatigue (but not physical or emotional). Further, the indirect effect of mistreatment on intentions to leave the profession due to the pandemic was weakest for nurses with an internal work locus of control, suggesting that nurses who view their job outcomes to be within their realm of control were less likely to consider leaving the profession as an indirect consequence of experiencing mistreatment during the COVID-19 pandemic. Given the increase in nurse turnover and global nursing shortages, nurses’ experience of patient and family mistreatment could be an important point of intervention in attempting to promote nurse retention during crisis events.</p>