Background The first-ever round of school-based mass drug administration (MDA) with praziquantel together with mebendazole targeting school-aged children in endemic districts was conducted in 2009 by the National Neglected Tropical Diseases Control Program. To evaluate the impact of the treatment regimen, a cross-sectional sentinel site survey was conducted 6 months post-MDA. Methods Fifteen sentinel schools from six highly endemic districts (according to data from national and pre-MDA surveys) with Schistosoma mansoni affecting over 50% of the population, and moderate to high prevalence of hookworms (> 20%). Approximately 30 children aged 9-14 years were selected from each school and stool samples (one per student) were examined by the Kato-Katz method. Results The overall prevalence (and intensity) in these sentinel sites pre-MDA of S. mansoni was 69.0% (170.8 epg), hookworm: 41.7% (71.7 epg), Ascaris lumbricoides: 1.8% and Trichuris trichiura: 3.8%. Six months post MDA, the findings were S. mansoni: 38.2% (47.3 epg) and hookworm: 14.5% (8.7 epg), representing a reduction from pre-MDA levels of 44.6% (65.2%) and 72.3% (87.9%) respectively. The proportion of children who were moderately or heavily infected with S. mansoni fell from 35.6% pre MDA to 9.9% post MDA. Conclusions Significant reduction in S. mansoni and hookworm infection was achieved by this first round MDA in school-going children in Sierra Leone. This reduction in infection burden can potentially contribute to a reduction of morbidity, such as anaemia, in these children.