Compassion fatigue is a condition unique to the human service occupations, characterized by a state of tension and preoccupation with the traumatized clients by re-experiencing traumatic events. With increased incidences of traumatic events both nationally and globally, the greater burden of care and after-care is usually borne by health care professionals. The objective of this study was to determine the predictive role of work setting in the development of compassion fatigue among health care professionals in Moi Teaching and Referral Hospital (MTRH) Eldoret, Kenya. The study was guided by Figley Model of Compassion Fatigue and adopted the Ex Post Facto research design. The target population was 76 doctors, 212 nurses and 33 counselors working in twelve units (grouped into more traumatizing and less traumatizing) offering specialized patient care services. A stratified simple random sampling technique was used to select a sample of 82 participants comprising of 19 Doctors, 54 Nurses and 9 Counselors. The independent variable was Years of Experience while Compassion Fatigue was the dependent variable. Data was collected using a demographic questionnaire, the "Professional Quality of Life Scale (ProQoL) version V". Data was analyzed using analysis of variance (ANOVA) and t-tests. All the inferential statistics were tested at 0.05 level of significance and data presented in form of percentages, frequencies and means while graphic presentation was in form of graphs. The result showed a statistically significant association between work setting and compassion fatigue with a t of 6.266 and a p of <0.05 on the basis of which the hypothesis was therefore rejected. Based on the findings of this study, it is recommended that professional licensing bodies such as Kenya Medical Association, Kenya Counseling and Psychologist Association, Nursing Council of Kenya which license doctors, counselors and nurses respectively should include wellness and impairment of care providers in their respective curricular.