Information on the extent to which oxidative stress and inflammation occur in the presence of falciparum malaria and type 2 diabetes mellitus in the same individual is limited. This study sought to investigate the extent of inflammation and oxidative stress in adult uncomplicated malaria by measuring fasting levels of lipid peroxides, C-reactive protein (CRP), and total antioxidant power (TAP) before and during falciparum malaria, in 100 respondents with type 2 diabetes and 100 age-matched controls in the Cape Coast metropolis of Ghana. Also, body adiposity index, body mass index, and waist-to-hip ratio were computed. Before and during falciparum malaria, diabetes patients exhibited higher (P < 0.05) levels of CRP and peroxides than controls but TAP and BAI were comparable (P > 0.05) between the two groups. Baseline CRP correlated positively (r = 0.341, P = 0.002) with peroxide only in the diabetic group. During malaria, TAP level in both study groups declined (P < 0.05) by 80% of their baseline levels. CRP correlated negatively (r = -0.352, P = 0.011) with TAP in the control but not the diabetic group. Uncomplicated falciparum malaria elevated inflammation and peroxidation but decreased antioxidant power independent of adiposity. This finding may have implication on cardiovascular health.