Introduction The objective was to study seroepidemiology and potential risk factors of Rift Valley Fever (RVF) virus infection in South Western Saudi Arabia.

Methods A random sample of the general population were studied. Through questionnaire interviews, data were collected regarding sociodemographic status, housing conditions, animal contact and other relevant information. Blood samples were taken and tested for RVF-specific IgG and IgM utilising enzyme-linked immunosorbent assays (ELISAs).

Results Out of 2322 persons included in the study, only 139 were positive for RVF-specific IgG giving an overall prevalence of 6.0%. On the other hand, none of the study samples were found to be sero-positive to RVF-specific IgM. The highest prevalence of sero positive RVF IgG was observed in Al Birk of Aseer region (13.3%) followed by Al-Arda of Jizan Region (11.8%), where the first animal deaths were reported during 2000–2001 outbreak. The study revealed zero prevalence of specific IgM and IgG among children born after the 2000–2001 outbreak. Using multivariate binary logistic regression analysis, the following significant risk factors were identified; lacking house electricity, having animals in the house, history of slaughtering animals, contact with or transporting aborted animals.

Conclusion The lack of recent virus activity mandates the rigorous maintenance of the control measures undertaken by the Ministries of Agriculture and Health. It is recommended to have regular seroepidemiological surveillance of RVF among humans, fostering public health messages in the region for risk reduction on reducing the risk of animal-to-human transmission as a result of unsafe animal husbandry and slaughtering practices.