Malaria caused by Plasmodium parasites remains a major global health problem, with 3.2 billion people estimated to be at risk of infection. In 2019, malaria infected an estimated 229 million people with 409 000 fatalities. The development of highly effective malaria vaccines is needed to leverage human immune responses and thus limit malaria mortality worldwide. However, this has been hampered by poor understanding of naturally acquired or vaccine-induced immunity. Here we assessed the single cell transcriptional profiles of PBMCs collected from malaria-infected children and adults as well as in-country healthy controls. The samples were collected during acute infection (Day0) and during convalescence (Day7 and Day28 after medication) After pre-processing, data normalization and integration, we obtained 106 000 cells from 19 samples from which we reconstructed 15 major cell clusters. Focusing on innate cell subsets, we found that CD14 Monocytes are more transcriptionally active than CD16 monocytes during malaria infection. Genes differentially expressed (DEGs) in monocytes and classical dendritic cells (cDCs) are enriched in myeloid cell activation and phagocytosis during acute infection, and antigen presentation during convalescence. CD16 monocytes and cDCs are enriched in inflammatory responses during acute infection. Promoters of DEGs in CD14 and CD16 monocytes (acute vs convalescence), are enriched in NF-κB-p65 which induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines. CD16 monocyte promoters are uniquely enriched in P53 binding sites. P53 has been shown to accentuate malaria-induced inflammation in monocytes which enhances protection against malaria fever. These data reveal innate cells are highly activated during acute infection as shown by the up-regulation of TOLL-LIKE RECEPTORS, up-regulating genes involved in phagocytosis including CR1, FCGR1A and CD36 and inflammatory responses including S100A8/9, further analysis will describe how these innate cells interact with adaptive immune cells i.e. T and B cells during malaria infection.