Thrombocytopenia is a common finding in malaria, but its prognostic value has not been addressed in children. The relationship between thrombocytopenia (platelet count < 100,000/mm3 on admission) and severity and outcome was investigated prospectively in children hospitalized with falciparum malaria in Dakar, Senegal, an area that is hypoendemic for malaria. Of 288 falciparum cases, 215 matched the 2000 World Health Organization definition of severe malaria. Median platelet counts were lower (98,000/mm3 versus 139,000/mm3; P < 0.02) among severe cases than in mild cases, and in children who died than among those who recovered (68,500/mm3 versus 109,000/mm3; P < 0.002). In severe cases, children presenting with a platelet count < 100,000/mm3 were more likely to die (odds ratio [OR] = 6.31, 95% confidence interval [CI] = 2.0-26.0). Moreover, multivariate analysis identified thrombocytopenia as an independent predictor of death (OR = 13.3, 95% CI = 3.2-55.1). Our data show an association between thrombocytopenia and either severity or prognosis in childhood falciparum malaria.