AbstractObjectiveMicroscopy was used to characterize platelet-Plasmodium-infected erythrocyte interactions in patients infected withPlasmodium falciparum,Plasmodium vivax,Plasmodium ovaleorPlasmodium malariae, and to investigate the relationship between platelet-associated parasite killing and parasite clearance.MethodsData from 244 malaria patients admitted to the Fourth People’s Hospital of Nanning between 1 January 2011 and 30 September 2022, and 45 healthy controls, were collected prospectively and assessed retrospectively. Characteristics of platelet–erythrocyte interactions were visualized by microscopy, and blood cell count and clinical profiles of these participants were obtained from the electronic medical records. ANOVA, contingency tables and Cox proportional hazards regression models were used to do statistical analysis on the subgroups.ResultsPlatelet enlargement and minor pseudopodia development were observed. Platelets were found directly attaching to parasitized erythrocytes by allPlasmodiumspecies studied, especially mature stages, and lysis of parasitized erythrocytes was connected to platelet-mediated cytolysis. Platelet counts were correlated inversely with parasitaemia and duration of parasite clearance. Artemisinin combination therapy was more effective than artemisinin alone in clearingPlasmodiumin patients with thrombocytopenia.ConclusionsPlatelet-parasitized erythrocytes cell-to-cell contacts initiated platelet-associated parasite killing and helped to limitPlasmodiuminfection in cases of human malaria. The weakening platelet-associated parasite killing effects could be counteracted by artemisinin combination therapy in patients with thrombocytopenia.