Folates are B vitamins that are required for the synthesis of nucleotides and amino acids, and for methylation reactions. Malaria is a parasitic infection with nearly 200 million cases per year. The parasite can obtain folate from its host or synthesize it de novo; this pathway has been a popular pharmacological target for anti-malarial therapies. In earlier work, we showed that mice with a deficiency of methylenetetrahydrofolate reductase, the enzyme that generates the active circulatory form of folate, (Mthfr^+/- mice) were protected against Plasmodium berghei ANKA infection (cerebral malaria) when they were fed standard mouse chow. These resistant mice had increases in total splenocytes, total T cells, CD4⁺ and CD8⁺ T cells, and in CCR4⁺ NK cells. With increased folate intake due to food fortification and vitamin supplementation in many countries, we questioned whether dietary folate would also affect the response to malarial infection in these mice. Mthfr^+/- and Mthfr^+/+ mice were fed amino acid- defined control diets (CD, recommended folate level) or folic acid-supplemented diets (FASD, 10-fold higher than recommended) for 5 weeks before infection with Plasmodium berghei ANKA. There was no survival difference between Mthfr^+/- or Mthfr^+/+ mice on these diets, but CD mice survived longer (p<0.01, log-rank test) and had lower parasitemia (p<0.05, t-test) compared with FASD mice. Resistant CD mice had higher numbers of total splenocytes, total T cells, as well as higher numbers of specific T and NK cell sub-populations (CD4⁺ T cells, CD4⁺ IFNγ⁺ T cells, CD8⁺ T cells, CCR4⁺ NK cells and CCR4⁺ IFNγ⁺ NK cells), compared with FASD mice (p<0.05, ANOVA). These differences due to diet are similar to those seen in our earlier study of genotype differences. Decreased brain TNFα immunoreactive protein (p<0.001, t-test) and decreased liver Abca1 mRNA (p<0.01, t-test), a modulator of TNFα, were observed in CD mice; these variables correlated positively (r_s= 0.58, p<0.01). Bcl-xl/Bak mRNA was decreased in liver of CD mice (p<0.0001, t-test), suggesting higher apoptotic potential. We conclude that genetic or dietary reduction in folates results in decreased parasite replication, an altered immune response and increased resistance to malaria in mice. These findings have relevance for malaria-endemic regions when considering anti-folate anti-malarials, food fortification, or vitamin supplementation programs.