Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are significantly elevated and of prognostic value in patients suffering from serious infectious diseases such as HIV and tuberculosis. Our objective was to investigate suPAR levels during symptomatic malaria infection and 7 days after treatment. Children younger than 6 years who presented with fever or other symptoms compatible with malaria were enrolled. Blood films and samples were collected on day 0 and day 7. Twenty-five children were allocated to each of three groups according to the amount of Plasmodium falciparum detected in their initial blood film. Children in group 1 had parasite densities in excess of 20 parasites per 200 leucocytes. The median plasma suPAR level was 6.49 ng/mL (interquartile range [IQR]: 4.90-7.61) and correlated to parasitemia (Spearman 0.43, P < 0.0001). Blood was obtained from 20 children in group 1 after 7 days of treatment. All became malaria negative in their blood slides and all decreased in suPAR level to median 3.48 ng/mL (IQR: 3.08-3.91) (P < 0.0001). Group 2 consisted of 25 children with 1-20 parasites in their blood slide. The suPAR level was median 2.91 ng/mL (IQR: 2.27-4.40) and decreased with median 0.5 ng/mL following treatment (P = 0.0002). Group 3 showed to be negative in their blood slides and most received antibiotic treatment. suPAR decreased from median 3.26 ng/mL (IQR: 2.77-4.46) to median 2.47 ng/mL (IQR: 2.01-3.75), on day 7 (P = 0.006). This study demonstrates an important association between suPAR and acute malaria infection in humans.