Sequestration of Plasmodium falciparum-infected erythrocytes (PfIE) in the capillaries of the central nervous system (CNS) is the pathognomonic feature of cerebral malaria, a condition frequently leading to death. Sequestration of PfIE in the placental intervillous spaces is the characteristic feature of malaria in pregnancy and is associated with low birthweight and prematurity. Although both patterns of sequestration are thought to result from the expression of different parasite proteins involved in cytoadhesion to human receptors, scant information exists on whether both conditions can coexist and whether this can lead to death. We conducted a prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary-level referral hospital in Maputo, Mozambique, between October 2002 and December 2006. Extensive sampling of all major viscera was performed. All cases showing parasites in any of the viscera were included in the analysis. From 317 complete autopsies PfIEs were identified in ten women (3.2%). All cases showed massive accumulation of PfIE in small capillaries of the CNS but also in most visceral capillaries (heart, lung, kidney, uterus). Placental tissue, available in four cases, showed a massive accumulation of maternal PfIE in the intervillous space. Coma (six women) and dyspnoea (five women) were the most frequent presenting clinical symptoms. In conclusion, massive visceral sequestration of PfIE with significant involvement of the CNS is an infrequent but definite direct cause of maternal death in endemic areas of Africa. The PfIE sequestered in cerebral capillaries and the placenta coexist in these fatal cases.