Signal regulatory protein (SIRP ) is an immunoreceptor expressed in myeloid innate immune cells that signals for inhibition of both phagocytosis and inflammatory response. Malaria parasites have evolutionarily selected multiple mechanisms that allow them to evade host immune defenses, including the modulation of cells belonging to innate immunity. Notwithstanding, little attention has been given to SIRP in the context of immunosuppressive states induced by malaria. The present study attempted to investigate if malaria parasites are endowed with the capacity of modulating the expression of SIRP on cells of innate immune system. Human peripheral blood mononuclear cells (PBMC) from healthy individuals were incubated in the presence of lipopolysaccharide (LPS) or crude extracts of P. falciparum or P. vivax and then, the expression of SIRP was evaluated by flow cytometry. As expected, LPS showed an inhibitory effect on the expression of SIRP in the population of monocytes, characterized by cell morphology in flow cytometry analysis, while Plasmodium extracts induced a significant positive modulation. Additional phenotyping of cells revealed that the modulatory potential of Plasmodium antigens on SIRP expression was restricted to the population of monocytes (CD14+CD11c+), as no effect on myeloid dendritic cells (CD14􀀀CD11c+) was observed. We hypothesize that malaria parasites explore inhibitory signaling of SIRP to suppress antiparasitic immune responses contributing to the establishment of infection. Nevertheless, further studies are still required to better understand the role of SIRP modulation in malaria immunity and pathogenesis.