BACKGROUND: Low density Plasmodium falciparum infections, below the microscopic detection limit, may play an important role in maintaining malaria transmission in low endemic areas as well as contribute to the maintenance of acquired immunity. Little is known about factors influencing the occurrence of sub-microscopic parasitaemia or the relation with immune responses.We investigated possible associations between the occurrence of sub-microscopic P. falciparum parasite carriage and antibody responses to the asexual stage antigens, G6PD deficiency and alpha+-thalassaemia in 464 subjects from a low endemic area in northern Tanzania. METHODS: We used samples collected from two cross sectional surveys conducted during dry and wet season in 2005. Submicroscopic parasitaemia was detected by using quantitative nucleic acid sequence based amplification (QT-NASBA). Genotyping for G6PD and alpha+-thalassaemia were performed by high throughput PCR; the prevalence and level of total IgG antibodies against MSP-1, MSP-2 and AMA-1 were determined by ELISA. RESULTS: Compared to parasite free individuals, individuals carrying sub-microscopic densities of P. falciparum parasites had significantly higher median antibody levels to MSP-1 (p = 0.042) and MSP-2 (p = 0.034) but not to AMA-1 (p = 0.14) while no clear relation between sub-microscopic parasite carriage and G6PD deficiency or alpha+-thalassaemia was observed. CONCLUSION: Our data suggest a role for sub-microscopic parasite densities in eliciting or maintaining humoral immune responses without evidence for a modulating effect of G6PD deficiency or alpha+-thalassaemia.