Current diagnosis of schistosomiasis is still not ideal. In the present study we evaluated a targeted affinity approach using mAb 114-4D12, reactive with a unique Schistosoma mansoni-specific glycan epitope, combined with matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry. For nine of 11 urine samples (1ml) from Egyptian individuals with different intensities of infection, a characteristic MALDI-TOF mass spectrum was observed, representing a series of fuco-oligosaccharides that are produced by schistosome eggs. The identification of these small molecule markers may lead to a new egg-load-related assay for light infections in schistosomiasis.