Background: Most studies that assess efficacy of antimalarial drugs focus on the outcome of clinical treatment. However, community surveys of surrogate indicators are often more practical and can provide a wider view of possible changes in drug response, but it has not been clear whether assessment of parasite isolates from patients and asymptomatic individuals are directly comparable. In the present work, we have compared the prevalence of molecular markers associated with resistance to sulfadoxine-pyrimethamine in parasites isolated from asymptomatic and symptomatic individuals. Methods: The study was conducted during April and May 2008 in Anonkoua-Koute (Abobo-Abidjan) in southern Cote d’Ivoire, an area where SP has been intensively used for more than 20 years. Plasmodium falciparum monospecific infection was detected by blood smears, followed by a genomic DNA extraction from blood spots on filter paper. Extracted DNA was amplified by nested-PCR, and pfdhfr and pfdhps sequences analyzed. Results: Ninety six of 107 asymptomatic schoolchildren sampled were positive for P. falciparum; 48 of these isolates were used for molecular analysis. A subset of 67 samples from malaria patients of school age was analyzed in parallel. For pfdhfr, the wild-type NCSI and the triple mutant IRNI alleles were both present in about 30 and 50% of the isolates from asymptomatic children and symptomatic malaria patients, respectively. For pfdhps, the symptomatic children mostly carried the single mutant genotype SGKAA although the double mutant AGKAA was the predominant allele in both populations. Conclusions: Direct comparison of molecular markers of SP resistance demonstrates that the prevalence of these alleles is comparable in isolates derived from asymptomatic and symptomatic individuals. The results from this study support the possibility of using cross sectional surveys of surrogate molecular markers of SP efficacy to inform decisions about choice of drugs for intermittent preventive treatment of pregnant women or seasonal malaria chemoprophylaxis.