Immune responses and clinical outcomes following infection and vaccination are highly variable between individuals. This is exemplified by human malaria infection, where variations in the kinetics or quality of the immune response can dictate whether the infection becomes asymptomatic or fatal. Recent advances in high-throughput omics technologies now allow immune responses to be interrogated in a highly dimensional and comprehensive manner. We utilised a controlled human malaria infection model and systems immunology to dissect the early immune response to infection with Plasmodium species and delineate the inter-individual variation in the mRNA and micro-RNA (miRNA) response to infection and parasite control. Our results demonstrate that blood stage infection with either P.falciparum and P.vivax malaria induced significant changes to whole blood mRNA and miRNA expression profiles. Unsupervised and supervised learning revealed significant heterogeneity in transcriptional and miRNA profile in volunteers before and 7-10 days after malaria infection. Genes and pathways associated with cytokine signaling, cytokine associated intracellular signaling pathways and activation were highly upregulated following infection with both species of malaria. Integrative analysis of mRNA and miRNA expression patterns revealed significant and novel relationships between mRNA and miRNA. Critically, we identified 10 specific miRNAs whose relative expression levels were significantly associated with differences in parasite multiplication rate (PMR) between individuals. This suggests that the miRNA expression pattern following infection may determine an individual’s ability to control parasitaemia. Taken together, these data to describe an integrative analysis of miRNA and transcriptional changes in human malaria infection. Importantly, we highlight a novel panel of miRNAs that are associated with the diverse responses to malaria infection, which could inform the development of more effective vaccinations.