In this study, antibodies (Ab) directed against three MSP antigens; MSP1(19), MSP2(A), and MSP2(B) were analyzed in blood samples obtained from 223 Sudanese patients who presented with either severe malaria (SM) or uncomplicated malaria (UM) and from 117 malaria-free donors (MF). The results showed that the prevalence of MSP Abs was associated with the clinical outcome of malaria infection, and the Ab prevalence was age-dependent (P<0.0005). More importantly, the prevalence of MSP Abs against the test antigens was lower in SM compared to UM (P=0.001 to 0.020), suggesting a protective role for these Abs against SM. Furthermore, the Ab responses between individual complications of SM were significantly different.