Abstract Background Acute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 ( Pf HRP2 ), as a measure of sequestered parasite burden, with AKI in severe malaria. Methods Admission plasma suPAR and Pf HRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n = 137). Patients were stratified according to AKI severity based on admission creatinine clearance. Results A total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into ‘mild, ‘moderate’ and ‘severe’ AKI groups, respectively. Plasma suPAR and Pf HRP2 concentrations increased with AKI severity (test-for-trend P