Complement (C) can be activated during malaria, C components consumed and inflammatory mediators produced. This has potential to impair host innate defence. In a case-control study, C activation was assessed by measuring serum haemolytic activity (CH50), functional activity of each pathway and levels of C3a, C4a and C5a in children presenting at Kisumu District Hospital, western Kenya, with severe malarial anaemia (SMA) or uncomplicated malaria (UM). CH50 median titers for lysis of sensitized sheep erythrocytes in SMA (8.6 U/mL) were below normal (34-70 U/mL) and were one-fourth the level in UM (34.6 U/mL (P < 0.001). Plasma C3a median levels were 10 times higher than in normals forSMA (3,200 ng/ml) and for UM (3,500 ng/ml), indicating substantial C activation in both groups. Similar trends were obtained for C4a and C5a. The activities of all three C pathways were greatly reduced in SMA compared to UM (9.9% vs 83.4% for CP, 0.09% vs 30.7% for MBL and 36.8% vs 87.7% for AP respectively, P < 0.001). These results indicate that, while C activation occurs in both SMA and UM, C consumption is excessive in SMA. It is speculated that in SMA, consumption of C exceeds its regeneration.