Malaria parasites possess a ‘plastid-like’ organelle called the apicoplast. Translation inhibitors that selectively target the apicoplast are lethal for the parasite. Several such compounds are clinically used as antimalarials, including doxycycline and clindamycin. However, parasites treated with an apicoplast inhibitor only arrest in their subsequent intra-erythrocytic development cycle, a characteristic known as the ‘delayed death’ effect.Treated parasites replicate once but transmit a defective apicoplast to their daughter cells. These progeny consequently cannot produce the sole essential metabolic product of the apicoplast in asexual blood stages: the isoprenoid precursor isopentenyl-pyrophosphate. However, it remains unclear what consequences isoprenoid depletion has on parasite cellular processes and how they contribute to parasite death. We have investigated the essentiality of isoprenoid compounds and characterised the molecular and morphological phenotype of delayed death. Metabolomic analysis together with fluorescence uptake experiments suggest that there is a disruption in digestive vacuole (DV) function and biogenesis in parasites undergoing delayed death. This is further supported by our analysis using serial block-face scanning electron microscopy, which shows that the DV fragments into multiple compartments in delayed death parasites and that these parasites also have abnormal uptake of the erythrocyte cytosol. We hypothesise that these phenomena arise from a defect in trafficking to the DV due to aberrant prenylation of vesicular trafficking proteins. Supplementing delayed death parasites with geranylgeraniol, an isoprenoid precursor used for protein prenylation, fully reverses the abnormal DV phenotype and temporarily rescues parasites for an additional infection cycle. This suggests that interruption of protein prenylation, and consequent cellular trafficking defects, are the proximal causes of delayed death.