Plasmodium falciparum is most commonly associated with severe malaria because it infects red blood cells of all ages, leading to higher levels of parasitemia. This results in the sequestration of infected erythrocytes in small blood vessels, causing microvascular obstruction, tissue hypoxia, and organ dysfunction. P. falciparum’s ability to cause cerebral malaria, severe anemia, and multi-organ failure distinguishes it from other species. These factors contribute to its higher mortality and severity compared to P. vivax, P. malariae, and P. ovale.

Reference: Harrison's Principles of Internal Medicine, Kasper et al., 20th Edition.