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In an effort to evaluate novel derivatives from artemisinin, possessing potential antimalarial activity, a new derivative artecyclopentyl mether (CPM-1) was derivatized and evaluated for its dose-dependent efficacy in Plasmodium yoelii nigeriensis infected mice. The survivability of mice at 7.5 mg/kg was >28 days with negligible parasitaemia and recovered anemia (66.16–72.62%). Artecyclopentyl mether was also found to modulate the pro- and anti-inflammatory cytokines (IFN-γ, 39.64–56.92%; TNF, 49.10–74.31%; IL-4, 11.53–43.22%; IL-10, 37.60–53.52%) favourably besides optimizing the oxidative stress to the infected subjects as evident by the nitric oxide (88.76–95.43%), lipid peroxidation (59.30–76.05%) and glycaemic data (62.70–76.66%). The results indicate the potentiality of the new derivative as an antimalarial against asexual stages of the parasite.