Splenic filtration of Plasmodium falciparum-infected red blood cells has been hypothesized to influence malaria pathogenesis. We have developed a minimum cylindrical diameter (MCD) filtration model which estimates physical splenic filtration during malaria infection. The key parameter in the model is the MCD, the smallest tube or cylinder that a red blood cell (RBC) can traverse without lysing. The MCD is defined by a relationship between the RBC surface area and volume. In the MCD filtration model, the MCD filtration function represents the probability of a cell becoming physically removed from circulation. This modelling approach was implemented at a field site in Blantyre, Malawi. We analysed peripheral blood samples from 120 study participants in four clinically defined groups (30 subjects each): cerebral malaria, uncomplicated malaria, aparasitaemic coma and healthy controls. We found statistically significant differences in the surface area and volumes of uninfected RBCs when healthy controls were compared with malaria patients. The estimated filtration rates generated by the MCD model corresponded to previous observations in ex vivo spleen experiments and models of red blood cell loss during acute malaria anaemia.There were no differences in the estimated splenic filtration rates between cerebral malaria and uncomplicated malaria patients. The MCD filtration model estimates that at time of admission, one ring-stage infected RBC is physically filtered by the spleen for each parasite that remains in peripheral circulation. This field study is the first to use microfluidic devices to identify rheological diversity in RBC populations associated with malaria infection and illness in well-characterized groups of children living in a malaria endemic area.