This study determined how well parasite density estimates by microscopy, qPCR and PfHRP-2 correlate to malaria severity. Patients aged ≤ 5 yrs with severe (n = 60, Hb ≤ 6 g/dl) and mild (n = 60, Hb > 6 g/dl) malaria were enrolled to take part in a case control study at Kisumu District Hospital, Western Kenya. Parasite load was determined by microscopy, qPCR targeting the 18s rRNA gene and PfHRP-2 antigen ELISA. The median parasite load and the 25th and the 75th percentile by microscopy in children with severe malaria (SM) was 49,958 parasites/μl (12,013-128,695) compared to 24,233 (6,122-103,886) in the group with mild malaria (MM), P = 0.10. By qPCR, the translated median parasite density was 31,550 parasites/μl (4,106-196,640) in the SM group compared to 24,365 parasites/μl (5,512-93,401) in the MM group (P = 0.73). According to PfHRP-2, the translated median parasite load in children with SM was 628,775 parasites/μl (332,222-1.165x106) compared to 150,453 (94,292-399,100) in children with MM (P < 0.0001). Unlike microscopy and qPCR, the parasite load detected by PfHRP-2 correlates with disease severity. Because of its unique attributes, PfHRP-2 is able to account for trophozoites and schizonts that are sequestered away from peripheral circulation. Because it persists in circulation, it also serves as an indicator of the magnitude of current and recent infections.