Abstract Background Continuous increase in drug resistance has hindered the control of malaria infection and resulted in multi-drug-resistant parasite strains. This, therefore, intensifies the search for alternative treatments with no or less side effects. Several histone deacetylase inhibitors have been characterised to possess anti-malaria activity; however, their further development as anti-malaria agents has not recorded much success. The present study investigated the anti-plasmodial activity of sodium acetate in Plasmodium berghei-infected mice, aiming at finding a better alternative source of malaria chemotherapy. Methods Thirty female Swiss albino mice were randomly distributed into six groups. Groups A (uninfected control) and B (infected control) received only distilled water. Group C (artesunate control) were infected and treated orally with 4 mg/kg artesunate on the first day, and subsequently 2 mg/kg artesunate. Groups D, E and F were infected and orally treated with 50, 100 and 200 mg/kg sodium acetate, respectively. Results Sodium acetate significantly lowered parasitaemia (p<0.05) after 4 days post-treatment, and the parasite inhibition rate of 68.5% at 50 mg/kg compared favourably with the 73.3% rate of artesunate. Similarly, administration of 50 mg/kg sodium acetate improved serum total cholesterol relatively better than artesunate. Our results also revealed that sodium acetate does not interfere with liver function, as there was no significant difference (p>0.05) in the serum activities of aspartate aminotransferase and alanine aminotransferase in both infected treated and uninfected mice. Conclusions This study shows that sodium acetate may be a safe alternative source of anti-malaria drugs. Its effect on the serum total cholesterol also predicts its ability in correcting malaria-induced metabolic syndromes.