Plasmodium falciparum is the parasite that causes the most severe form of human malaria. The disease manifests when P. falciparum invades and replicates in red blood cells (RBCs). From inside the RBC, the parasite can secrete small molecules, proteins and vesicles into the extracellular environment. These extracellular factors have been found to activate host immune and endothelial cells in vitro. However, biochemical changes in bystander, uninfected RBCs (essential for the continuation of the parasite lifecycle) have not been described. We performed untargeted metabolomics to characterise the metabolism of uninfected RBCs exposed to media from a P. falciparum culture (“conditioned unRBCs”) compared to control unRBCs. We observed significant perturbations to glycolysis in conditioned unRBCs, with few significant changes in other metabolic pathways. To evaluate active glycolytic flux in conditioned unRBCs, stable isotope labelled glucose (13C-glucose) was spiked into the cultures 3 h prior to metabolite extraction. Our data showed a distinct metabolic signature in conditioned unRBCs whereby 13C-pyruvate and 13C-lactate (the end products of glycolysis) accumulated and upstream 13C-metabolite isotopologues were depleted, reflecting an overall increase in glycolytic flux. Notably, 13C-bisphosphoglycerates, which are important for regulating dissociation of oxygen from haemoglobin, were depleted in conditioned unRBCs. To identify the parasite factors driving these perturbations, media from a P. falciparum culture was filtered to remove protein and extracellular vesicles, and incubated with unRBCs. We observed that the remaining parasite small molecules, alone, were capable of causing metabolic perturbations in unRBCs. Metabolomic profiling of media from P. falciparum cultures has provided a candidate list of small molecules that may be responsible for this effect. Altogether these data demonstrate that P. falciparum extracellular factors impact unRBC metabolism, which may contribute to the metabolic symptoms of malaria such as hypoglycaemia, lactic acidosis and anaemia.