BACKGROUND: Nurses' health status significantly impacts their well-being and patient safety. Workflow interruptions, perceived workload, and missed nursing may potentially affect their physical and mental health. However, there is currently a lack of systematic studies on the relationships between these factors. OBJECTIVE: This study aims to explore how workflow interruptions influence nurses' health status through perceived workload and missed nursing, and provide strategies to promote nurses' health. METHODS: In October 2024, an online survey was conducted among 646 clinical nurses from three healthcare facilities in Henan Province. The survey covered nurses' demographic information, workflow interruptions, health status, perceived workload and missed nursing. Statistical analysis and model construction and validation were performed using SPSS 25.0 and AMOS 26.0 software. RESULTS: Workflow interruptions were significantly negatively correlated with both physical component summary and mental component summary. Perceived workload and missed nursing served as mediators between workflow interruptions and physical and mental component summaries. CONCLUSION: Workflow interruptions directly affect nurses' health status and indirectly influence it through perceived workload and missed nursing. Therefore, strategies should be implemented to optimise workflows, reduce workflow interruptions, lower perceived workload and take measures to minimise missed nursing. Future research could explore how to implement workflow optimization to improve nurses' health status effectively. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This study provides important guidance for improving nurses' health. The results reveal that optimising workflow and reducing work interruptions can effectively reduce nurses' perceived workload, thereby decreasing the occurrence of nursing omissions, and ultimately contributing to the overall improvement of nurses' health. REPORTING METHOD: This study adhered to the cross-sectional Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.