In malaria endemic areas intermittent treatment with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in pregnancy. Yet, data on perceptions regarding use of this drug are scarce. An exploratory study was conducted to assess perceptions on SP in Mukono district, Uganda. This is an initial step towards a review of the policy aimed at improving access and use of SP in pregnancy, which is currently low. Results show that SP is perceived to be an effective drug that cures malaria quickly. However there are negative perceptions related to its use in pregnancy. SP is believed to be strong and weakens pregnant women, causes abortions and foetal abnormalities. There is also a perception that resorting first to SP for malaria treatment may lead to the development of drug resistance. This perception may limit access to effective treatment of malaria in this community since the policy in Uganda recommends SP in combination with chloroquine as the first-line treatment. The policy implications of these findings include developing a health promotion package to demystify the misconceptions on the strength of SP, to explain its benefits and side-effects. This package will involve giving health workers refresher training on communication and counselling on use of SP in pregnancy targeting special groups like pregnant adolescents. These results provide important lessons to policy makers and programme managers who aim at scaling up access of SP for malaria prevention in pregnancy.