Introduction. Malaria is a leading cause of mortality among children below 5 years in Ghana. Its parasites are known to cause the degradation of hemoglobin, resulting in the production of reactive oxygen species and hence oxidant stress. Therefore, this study was carried out to compare the levels of oxidative stress between children with complicated and uncomplicated malaria infection in Kumasi, Ghana. Method. Subjects were recruited from hospitals in the Kumasi Metropolis. This was a cross-sectional study, involving 17 complicated malaria subjects, 51 uncomplicated malaria subjects, and 15 nonparasitemic subjects. The rapid diagnostic test (RDT) was used to determine presence or absence of falciparum malaria among the study participants. Blood samples from subjects were used to determine hemoglobin, malondialdehyde (MDA), and vitamin C levels. Results. Majority of the subjects (67.5%) were within the age of 0-5 years. The mean age (±SD) of uncomplicated malaria subjects was 4.32 (±2.81) years, while that of complicated malaria was 4.27 (±2.96). Mean levels of HB decreased significantly in the following order: control subjects > uncomplicated malaria subjects > complicated malaria subjects (p<0.0001). Mean levels of MDA were significantly lower in control subjects compared to complicated malaria subjects (4.62±1.85 versus 6.68±0.70, p=0.0008) and also lowered in uncomplicated malaria subjects compared to complicated malaria (4.50±1.58 versus 6.68±0.70, p<0.0001). There was a statistically significant reduced mean level of vitamin C (p=0.036) in the following order: control subjects > uncomplicated malaria > complicated malaria subjects. However, for the complicated malaria cases, there were significantly higher mean vitamin C levels in females than in males (p<0.001). Conclusion. Malaria progression increases MDA levels and decreases the ascorbate (vitamin C) and hemoglobin levels. It is recommended that future studies should investigate changes in other antioxidant vitamins, like vitamins A and E.