Presenteeism is linked to negative outcomes for patients, nurses, and health care organizations; however, we lack understanding of the relationships between nurse fatigue, burnout, psychological well-being, team vitality, presenteeism, and patient safety in nursing. Therefore, the two aims of this study were: (a) to examine the fit of a literature-derived model of the relationships between presenteeism, psychological health and well-being, fatigue, burnout, team vitality, and patient safety; and (b) to examine the role of presenteeism as a mediator between patient safety and the other model variables. Survey data were analyzed using Composite Indicator Structural Equation (CISE) modeling, a type of structural equation modeling. Model fit was acceptable with multiple significant relationships. Presenteeism due to job-stress mediated multiple relationships to patient safety. Our findings indicate that focusing on job-stress presenteeism may be relevant for this population and may offer additional insight into factors contributing to decreased nurse performance and the resulting risks to patient safety.