AbstractObjectiveTo determine whether the positive results of a single-district pilot project focused on rectal artesunate administration at the community level in Zambia could be replicated on a larger scale.MethodsIn partnership with government, in 10 rural districts during 2018–2021 we: (i) trained community health volunteers to administer rectal artesunate to children with suspected severe malaria and refer them to a health facility; (ii) supported communities to establish emergency transport, food banks and emergency savings to reduce referral delays; (iii) ensured adequate drug supplies; (iv) trained health workers to treat severe malaria with injectable artesunate; and (v) monitored severe malaria cases and associated deaths via surveys, health facility data and a community monitoring system.ResultsIntervention communities accessed quality-assured rectal artesunate from trained community health volunteers, and follow-on treatment for severe malaria from health workers. Based on formal data from the health management information system, reported deaths from severe malaria reduced significantly from 3.1% (22/699; 95% confidence interval, CI: 2.0–4.2) to 0.5% (2/365; 95% CI: 0.0–1.1) in two demonstration districts, and from 6.2% (14/225; 95% CI: 3.6–8.8) to 0.6% (2/321; 95% CI: 0.0–1.3) in eight scale-up districts.ConclusionDespite the effects of the coronavirus disease, our results confirmed that pre-referral rectal artesunate administered by community health volunteers can be an effective intervention for severe malaria among young children. Our results strengthen the case for wider expansion of the pre-referral treatment in Zambia and elsewhere when combined with supporting interventions.