Background Rectal artesunate (RAS), an efficacious pre-referral treatment for severe malaria in children, was deployed at scale in Uganda, Nigeria and DR Congo. In addition to distributing RAS, implementation required additional investments in crucial but neglected components in the care for severe malaria. We examined the real-world costs and barriers to RAS implementation. Methods We collected primary data on baseline health system gaps and subsequent RAS implementation expenditures. We calculated the equivalent annual cost of RAS implementation per child under 5 at risk of severe malaria, from a health system perspective, separating neglected routine health system components from incremental RAS introduction costs. Findings The largest baseline gaps were irregular health worker supervisions, inadequate referral facility worker training, and inadequate malaria commodity supplies. Health worker training and behaviour change campaigns were the largest startup costs, while supervision and supply chain management accounted for most annual routine costs. The equivalent annual costs of preparing the health system for treating severe malaria with RAS were $2.31, $2.20 and 4.15 per child at risk in Uganda, Nigeria and DRC. The incremental costs of introducing RAS, net of routine neglected components, accounted for a minority at $0.72, $0.59 and $0.94. Interpretation While RAS has been touted as a cost-effective pre-referral treatment for severe malaria in children, its real-world potential is limited by weak and under-financed continuums of care. Scaling up RAS or other interventions relying on community healthcare providers only makes sense alongside additional, essential health system investments sustained over the long-term. Funding Unitaid