Schistosomiasis, a disease caused by Schistosoma trematode parasites, affects hundreds of millions of people and accounts for more than 40% of the global health burden due to neglected tropical diseases. In Uganda, intestinal schistosomiasis is endemic in 73 out of 112 districts and about 55% of the population of 36 million individuals are at risk. There is scanty information on the status and burden of schistosomiasis in preschool children less than six years of age in Uganda. This study aimed to assess the status of Schistosoma mansoni infections in children aged 1-5 years in Uganda. S. mansoni prevalence and intensity of infection were examined in 3058 children from 5 districts along Lake Victoria shoreline, eastern Uganda. For each child one stool sample was collected on three consecutive days. The Kato-Katz technique was used to prepare stool smears on slides for microscopic examination. Short interviews with a standardized pre-tested questionnaire prepared in the local language (Lusoga) were administered to each caregiver to identify risk factors associated with S. mansoni infection. An overall S. mansoni prevalence of 39.3% (95% CI: 38.0-41.1%) was estimated out of the 3058 stool samples examined. The geometric mean intensity of S. mansoni among the infected children was 273 (95% CI: 241-305) eggs per gram of faeces. Both prevalence and intensity of infection increased linearly with age (P<0.0001) and were highest in the age group 49-60 months. Majority (61%) of the children, especially in the age group 12-24 months (84.2%; 95% CI: 75.6-90.1%), were lightly infected. Short interviews with caregivers revealed that preschool children, 1-5 years old, get exposed to S. mansoni infested waters through bathing, playing or swimming. It is important that the Uganda national control programme for schistosomiasis takes preschool children into consideration and that health education on transmission of schistosomiasis is delivered to the endemic communities regularly.