Résumé : Objective  To assess the effect of intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp-SP) on birth weight in sites with varying degrees of drug resistance.Methods  Birth weight data from three regions in Democratic Republic of Congo with varying degrees of sulfadoxine–pyrimethamine (SP) resistance (1.6% in Mikalayi, 21.7% in Kisangani and 60.6% in Rutshuru) were analysed retrospectively by means of a logistic model that included the number of SP doses taken by the mother and other potentials confounding factors.Results  The IPTp-SP reduced the risk of low birth weight (LBW) in Kisangani (adjusted OR, 0.15; IC95%, 0.05–0.46) and in Mikalayi (adjusted OR, 0.12; IC95%, 0.01–0.89). In both sites, the average birth weight was higher for mothers having received two rather than one or no SP doses (P < 0.001). In Rutshuru, IPTp-SP had an effect in primigravidae but not in multigravidae. However, after adjustment for other LBW risk factors, there was no difference in the proportion of LBW (adjusted OR 0.92; IC95%, 0.37–2.25) between women having taken at least 2 SP doses and those with only one dose or none.Conclusion  IPT-SP remains an effective strategy in Kisangani and Mikalayi where the therapeutic failure to SP in children with clinical malaria was 21.7% and 1.6%, respectively, while IPTp-SP effect seems lower in Rutshuru where the therapeutic failure to SP was 60.6%. The threshold value of SP resistance at which IPTp-SP fails to have a significant impact on birth weight and LBW is unknown. Considering that no alternative is currently available, additional studies on the efficacy of IPTp-SP in the areas of high SP resistance such as Rutshuru are needed so that the threshold at which this intervention fails to provide any benefit is determined with some precision.