Background: Information on the relationship between host genetic factors and susceptibility to malaria has been partially evaluated. Host receptors (CD36) has been shown to have a role in the innate immune response to malaria, but the mechanism on how the host receptors affect immune response has not been described. Methodology: This study was conducted in Magugu, Manyara region along the Northern Rift Valley area of Tanzania to determine the effect of CD36 deficiency on prevalence and levels of anti-MSP1-19 IgG antibodies and its association with malaria in children. A c.1264 T>G of the CD36 gene mutation which leads to CD36 deficiency was studied. A longitudinal study was conducted to investigate whether the presence or absence of the CD36 molecule on immune cells has an effect on anti-MSP1-19 antibodies production and how this is reflected clinically. A total of 249 children aged 2-12 years were genotyped for the CD36 gene. Results: Genotyping results shows that out of 249 children for the CD36 gene (c.1264 T>G) mutation, only 3 (1.2%) were homozygous for the mutation, 9 (3.6%) were heterozygous children and 237 (95.2%) were wild-type children. It was found that in both wild-type and heterozygous children, anti-MSP1-19 IgG antibody seropositivity increased from the baseline to the final surveys, thus wilt-type seropositivity increased from 53 (22.5%) in the baseline survey to 112 (47.5%) in the final survey. Like wise, seropositivity increased from 2 (22.2%) to 6 (66.7%) in the heterozygous genotype. However, there was no change in seropositivity to MSP1-19 between the baseline and final survey in homozygous children (p<0.01). The overall malaria prevalence was 18 (7.2%). Heterozygous children had statistically higher malaria incidence of 5 (55.6%) while the wild-type children had the lowest 12 (5.1%), malaria incidence was 1 (33.3%) in CD36 deficient children (p<0.01). Conclusion: First CD36 deficiency (homozygosity for the c.1264 T>G mutation) suppress IgG prevalence against MSP1-19. Second, CD36 deficiency predisposes children to clinical malaria through suppression of immune responsiveness to malaria parasites. Third, despite an increase of seropositivity to MSP1-19 in the heterozygous genotype, the antibodies were not protective to clinical malaria as malaria incidence in this genotype was also high compared to the wild=type children. Lastly, carriers of the c.1264 T>G mutation (homozygous and heterozygous children) were more predisposed to clinical malaria incidences as compared to the wild-type children.