For this study, we examined the nature of the unique relationships trait-negative affect and compassion satisfaction had with compassion fatigue and its components of secondary traumatic stress and burnout in 273 nurses from 1 metropolitan tertiary acute hospital in Western Australia. Participants completed the Professional Quality of Life Scale (Stamm, 2010), Depression Anxiety Stress Scale (Lovibond & Lovibond, 2004), and the State-Trait Anxiety Inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983). Bivariate correlation and hierarchical regression analyses were performed to examine and investigate 4 hypotheses. The results demonstrate a clear differential pattern of relationships with secondary traumatic stress and burnout for both trait-negative affect and compassion satisfaction. Trait-negative affect was clearly the more important factor in terms of its contribution to overall compassion fatigue and secondary traumatic stress. In contrast, compassion satisfaction's unique protective relationship only related to burnout, and not secondary traumatic stress. The results are therefore consistent with the view that compassion satisfaction may be an important internal resource that protects against burnout, but is not directly influential in protecting against secondary traumatic stress for nurses working in an acute-care hospital environment. With the projected nursing workforce shortages in Australia, it is apparent that a further understanding is warranted of how such personal variables may work as protective and risk factors.