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Abstract Aims This study aimed to examine sleep disturbance as a mediator of the relationship between professional quality of life (compassion satisfaction, burnout, secondary traumatic stress) and health (physical and mental health) in nurses. Design Descriptive, cross‐sectional study. Methods Three hundred eighteen Registered Nurses completed a web‐based survey at the National Institutes of Health Clinical Center in the United States. Mediation analyses were conducted to test hypothesized relationships. Results Nurses with higher levels of compassion satisfaction reported lower levels of sleep disturbance and better physical/mental health. Burnout and secondary traumatic stress were negatively associated with physical/mental health and positively associated with sleep disturbance. Sleep disturbance fully or partially mediated the relationships between professional quality of life and physical/mental health among nurses.