Background: The current study estimated (a) the indirect costs associated with non-fatal disability and premature death across a wide range of diseases and health conditions in Africa in 2015 and (b) the potential savings that could be accrued if countries were to meet the 3 health targets of the substainable development goal (SDG) compared to the costs under the status quo. Methods: This study used the lost output or human capital approach to quantify the gross domestic product (GDP) losses associated with the disability-adjusted-life-years (DALYs) lost due to all causes by age group as well as by country economic classification (Group 1: 10 high/upper-middle income countries; Group 2: 17 lower-middle income countries; and Group 3: 27 low income countries). Results: The expected indirect cost of the 704,765,879 DALYs lost in Africa in 2015 was Int$ 2,983,187,560,197. Of this amount, 25.17%, 57.84% and 16.99% were incurred by the economies of the countries comprising Group 1, Group 2 and Group 3, respectively. Of the total continental indirect cost, 36.9%, 10.5%, 13.7%, 17.0%, 7.6%, 6.8% and 7.5% were associated with people aged 0-4, 5-14, 15-29, 30-49, 50-59, 60-69 and 70 years or older, respectively. Most of the total indirect cost (56.61%) was attributable to maternal conditions, AIDS, tuberculosis (TB), malaria, neglected tropicald diseases (NTDs), non-communicable diseases and traffic injuries. Approximately half (47%) of this cost could be avoided (or saved) every year if the 3 (health) targets of the SDG were fully met. Conclusion: The study estimated the total indirect cost of illness due to all causes by age group and country economic classification. The annual indirect cost is substantial. The findings contained in this paper suggest that health system strengthening should focus on both rich and poor countries, people of all ages and specific disease categories.