In much of sub-Saharan Africa (SSA), malaria remains a key cause of paediatric hospital admission, and makes a substantial contribution to under 5-year mortality, estimated at 600,000 deaths annually. Despite implementing currently effective, fast-acting artemisinin-based combination therapies inpatient mortality for paediatric severe malaria remains unacceptably high at ~8%. The Severe malaria in Africa Research and Trials consortium-Master Adaptive Platform Trial (SMAART-MAP trial (ISRCTN79071535)) is a multi-country trial enrolling children aged >3 months and < 12 years who are admitted to hospital with evidence of Plasmodium falciparum malaria (slide or rapid diagnostic test (RDT) positive and one of the following complications: cerebral malaria (One or more reported seizures with altered consciousness (Blantyre Coma Score, BCS ≤ 4) or presence of coma (BCS ≤2); severe anaemia (haemoglobin <6 g/dl) or renal impairment (creatinine >1.5 upper limited of normal). The platform trial is simultaneously evaluating three adjunctive therapies in Phase II trials across SSA, addressing interventions against specific severe malaria complications, specifically, 1) Seizure prophylaxis with levetiracetam for children presenting with cerebral malaria; 2) Whole blood or red cell concentrates transfusion for children presenting with severe anaemia and 3) renal protection with paracetamol (15 mg/kg every 6 hours) in children with renal impairment. The trial is being run in eight hospitals across six African countries (Ghana, Democratic Republic of Congo, Uganda, Kenya, Zambia and Mozambique). Each trial has an early (~72 h) biomarker or clinical therapeutic efficacy endpoint based on putative mechanisms of action. The overarching goal is to identify the most promising interventions to take forward into a large Phase III/IV mortality endpoint trial.