Background: In the acute medical care hospital setting, nursing the sick and dying is both physically and emotionally demanding, making acute medical care hospital nurses more vulnerable to Compassion Fatigue (CF) or Secondary Traumatic Stress (STS). If not addressed in its earliest stages, CF can adversely change the caregiver's ability to provide compassionate care. It has been shown that Self-Compassion (SC) can be beneficial for the caregiver, with corresponding benefits for the individual needing care. However, the relationship of this attribute to CF in the acute medical care hospital nursing setting has not been intensively studied. This study explores the environmental and psychosocial factors affecting the prevalence and levels of CF in acute medical care hospital nursing staff and whether SC can be used as a coping strategy that enables nurses to mitigate the prevalence and levels of CF. Methods: Using a mixed-methods study design, acute medical care hospital nurses were surveyed using a demographic/ work-related questionnaire, the Secondary Traumatic Stress Scale (used to measure CF), the Self-Compassion Scale, questions requiring a narrative written response and semi-structured informal interviews. One-way ANOVA was conducted to explore the impact of work-related and demographic characteristics on levels of SC and CF. Pearson correlation co-efficient (r value) was used to explore the relationship between CF and SC and lastly, multiple regression was used to discover whether a predictive relationship existed between SC and CF. The interviews were recorded, transcribed verbatim and subjected to thematic analysis.