Objective To investigate the level and determinants of self-regulatory fatigue of nurses, and to provide reference for targeted intervention. Methods A total of 942 clinical nurses were investigated by using the general information questionnaire, Self-Regulatory Fatigue Scale, Chinese Nurses′ Job Stressors Scale, Connor-Davidson Resilience Scale, Perceived Organizational Support Scale and Social Support Rating Scale. Results The median score of self-regulatory fatigue was 47.00, with the quartiles of 43.00 and 51.00. Multiple linear regression analysis showed that organizational support, management and interpersonal problems, and the utilization of social support were influencing factors of nurses′ self-regulatory fatigue (P<0.01 for all). Conclusion The self-regulatory fatigue of nurses is at moderate to high level, so nursing managers should pay more attention to and take targeted interventions to enhance nurses′ self-regulation ability, thus to alleviate their fatigue.