SummarySchistosomiasis is a major cause of morbidity and mortality and has been estimated to infect over 200 million people. Diagnosis of schistosomiasis by detection of specifi c antibodies is likely to be more sensitive than the traditional method of diagnosis by detection of eggs in stool or urine. Therefore the present study was the fi rst attempt to highlight the seroepidemiology of schistosomiasis among the general population of Najran City, southern of Saudi Arabia, as well as to achieve the performance of the diagnostic tests used. A total of 180 participants attending King Khaled hospital in Najran Province, Saudi Arabia, over a one year period, from September 2013 to September 2014 were screened for the presence of Schistosoma antibody in their blood serum using an indirect hemagglutination assay (IHA). Specifi c immunoglobulin (Ig) G antibody was evaluated using an enzyme-linked immunosorbent assay (ELISA). Out of the 180 samples of sera tested using IHA, 32 (20 %) were found to be positive with a titer ranging from 1:160 to 1:1280, while 42(23.2 %) revealed Schistosoma IgG. A positive relationship was found between the seroprevalence of schistosomiasis and age of tested participants, especially in the age group of 20-40 years old. Additionally, prevalence of infection was more in males (36 %) than females (7.5 %), and showed statistical significance (P < 0.001). Similarly, there was signifi cant association between the presence of Schistosoma antibodies and the nationality of residence, and education of participants (P < 0.05). The current investigation reveals an alarmingly high prevalence of schistosomiasis among participants in Najran, southern region of Saudi Arabia and this supports an urgent need to re-evaluate the current control measures and implement an integrated, targeted and effective schistosomiasis control measures.