Burnout is a psychological syndrome resulting from repeated stressors experienced in the workplace that centers on emotional exhaustion, detachment from the job, and a sense of ineffectiveness. It has been previously demonstrated that burnout exists in the health care workforce, but there has been limited investigation of burnout in nurses who primarily provide care for patients who have been traumatically injured. The purpose of this study was to explore factors associated with burnout reported by trauma nurses. This was a secondary analysis of a cross-sectional survey distributed at a large, academic Level I trauma center that serves both adult and pediatric patients. For this analysis, only the Burnout subscale of the Professional Quality of Life scale Version 5 (ProQOL) was used. Multivariate hierarchical regression was used to determine factors associated with burnout reported by trauma nurses. Protective factors included being female, being married, and better quality of sleep. Risk factors included having a mental health diagnosis and working with adult populations. These results provide an important contribution to the burnout risk profile for trauma nurses and may provide insight into future investigations as well as development and testing of tailored interventions to mitigate burnout in trauma nurses.