Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR‐binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full‐length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1‐EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction. Synopsis Plasmodium falciparum parasites anchor infected erythrocytes to blood vessel walls using diverse PfEMP1 adhesion proteins. Severe malaria is caused by parasites expressing a particular type of PfEMP1, which if identified could lead to development of a disease reducing adjunctive drug or vaccine intervention. Full‐length sequences of PfEMP1 encoding transcripts were characterized in 44 children admitted to hospital with varying degrees of malaria pathology. Genes encoding PfEMP1 predicted to bind human endothelial protein C receptor (EPCR) through their CIDRα1 domains dominated PfEMP1 transcript profiles of children suffering from cerebral malaria and/or severe malarial anaemia. No other PfEMP1 domain or domain composition was associated with severe malaria. These observations support the feasibility of pursuing a malaria‐reducing vaccine or drug, which interferes with the PfEMP1–EPCR interaction. Plasmodium falciparum parasites anchor infected erythrocytes to blood vessel walls using diverse PfEMP1 adhesion proteins. Severe malaria is caused by parasites expressing a particular type of PfEMP1, which if identified could lead to development of a disease reducing adjunctive drug or vaccine intervention.