The purpose of this study was to explore and compare the levels of distress and burnout among Sudanese and Tanzanian health professionals. Cluster random sampling was used to select 72 nurses and physicians of both genders from each country. The participants’ age range was 21 years to 55 years (M_age = 31.51, SD = 7.22). The Maslach Burnout Inventory-Human Services Survey and the General Health Questionnaire were used to collect data. Nonpsychotic psychiatric disorders were more prevalent among Tanzanian health professionals compared to their Sudanese counterparts. T-test results revealed that Tanzanian health professionals experienced significantly higher levels of distress, somatic symptoms, depression, and social dysfunction than their Sudanese counterparts. ANOVA and MANOVA results indicated significant demographic differences in distress and burnout between health professionals from both countries. In addition, Sudanese participants reported higher levels of emotional exhaustion and lower personal accomplishment, while Tanzanians reported higher levels of depersonalisation. It was concluded that nurses from both countries were more prone to distress, while physicians were more susceptible to burnout. Our findings may assist researchers and administrators to improve the mental health of health professionals, particularly in Africa, and enhance their ability to provide better services.