Neutrophils, a heterogenous cell group, play an essential role in clearing many infectious pathogens. Mounting evidence suggests that neutrophils may play a central role in antibody-mediated naturally acquired and vaccine-induced immunity to malaria. Currently, there is very little known about the phenotypes and functions of neutrophils in human malaria infection. We investigated neutrophil phenotypes in in vitro models of direct neutrophil-malaria parasite interactions and a clinical trial of experimental human malaria. We examined Fcg-receptors and adhesion molecule expression involved in parasite killing and clearance. Flow cytometry analysis revealed no change in neutrophil phenotype in direct contact with un-opsonized malaria parasites. However, phagocytosis of antibody-opsonized parasites leads to distinct neutrophil functional phenotypes, characterized by changes in specific Fcg-receptor and adhesion molecule expression. These neutrophil phenotypes are different to typically activated phenotypes seen in bacterial infections and sepsis. In experimental human malaria, neutrophils showed early phenotypic and functional changes even at low parasitemia prior to clinical presentation. These data suggest an early influence of systemic mediators and/or cellular interactions on neutrophil functions. Furthermore, RNA-seq analysis revealed an upregulation of gene clusters relevant to neutrophil functional properties for clearance and killing of malaria parasites. Overall, our work identifies novel neutrophil phenotypes and functional changes in response to malaria parasites. This knowledge will be valuable to inform vaccine designs that maximize protective functions and understand why some vaccines fail in malaria-endemic populations.