Complicated malaria, caused by Plasmodium falciparum, is characterized by multiple organ dysfunction. The pathogenesis of complicated malaria involves complex host-parasite interactions that include polarized cytokine responses. Recently, correlates between Th1-like and Th2-like cytokines, especially interleukin-10 (IL), IL-12, and TNF-alpha, and specific types of organ dysfunction have been noted. Here, we measured IL-10, IL-12, and for the first time, IL-15, in 19 patients aged 16-55 years old with complicated malaria on days 0 (admission), 3, 7, and 14. For analysis, patients were grouped together or sub-categorized into hyperparasitemias or cerebral malaria (CM). For IL-10, a dramatic increase was noted on admission, followed by a reduction toward control values that closely paralleled parasite clearance. For IL-12, modest but persistent increases were noted over the entire 14 day period that did not correlate with parasitemia. In general, especially on days 0 and 3, hyperparasitemic patients had, in comparison with CM patients, higher IL-10 and IL-12 levels. In contrast, IL-15 was generally below detection in most samples. These results provide further insight into the pathogenesis of complicated malaria by strengthening the contention that cytokines such as IL-10 and IL-12 are involved in modulating the immune response to P. falciparum.