Background Stress is very common among medical students across the globe with the prevalence of 80%. In Ethiopia, the prevalence is 47.7% among college students. Unless it is managed early, it leads to deterioration of academic performance and overall dissatisfaction with life and different serious health problems including anxiety, depression, and suicide. The objective of this study is to assess the prevalence of academic related stress among Debre Birhan governmental and nongovernmental health science college regular students 2015/16. Method A cross-sectional study was conducted on a sample of 422 health science students selected by stratified proportional random sampling at Debre Birhan governmental and nongovernmental health science colleges in North Shewa zone, Amhara region, Ethiopia in 2016. Data was collected using the Depression Anxiety Stress Scaling (DASS-21). The level of significance of association for multivariable was determined at P value <0.05. Result Prevalence of stress among Debre Birhan governmental and nongovernmental health science college regular students is 4.1%. There is a significant association between stress and sex AOR = 8.525 (1.023, 71.077), fear of examination AOR = 5.096 (1.183, 21.96), living in uncomfortable environment AOR = 14.86 (3.84, 57.515), and perceived present illness AOR = .030 (0.003, 0.286). Depression and anxiety were also seen among 19.7% and 23.6%, respectively. Conclusion According to this study, the prevalence of stress among governmental and nongovernmental health science college regular students is not high. However, depression and anxiety were found to be higher than stress and they need immediate management plan. Colleges had better prepared simple screening tool and support students to prevent stress before they cause severe mental health problems.