Purpose: Brucellosis is responsible for considerable public health issues involving economic losses due to abortion, loss of milk production and infertility in adult males. The purpose of this study was to determine the sero-prevalence of brucellosis in Jazan Province, Saudi Arabia and assess the possible risk factors. Methods: An observational cross-sectional study was conducted in three geographical areas of Jazan Province, Saudi Arabia. The study sample included 400 participants from randomly selected primary health care centres. A standardised questionnaire was used to collect information on demographics and risk factors for brucellosis. A 5 ml blood sample was collected from each study participant. The SPSS statistical program was utilised for data analysis. Results: The overall sero-prevalence of brucellosis in Jazan Province was 13.4% and was higher among participants ≥ 40 years old (20%) than those < 40 years (12%). Prevalence was significantly higher among rural (39.3%; 95% confidence interval [CI], 29.8 – 49.7) than urban populations (4.6%; 95% CI, 2.7 – 7.9), in Saudis (14.5%; 95% CI, 11.1 – 18.8) than non-Saudis (3.0%; 95% CI, 7.0 – 15.3) and in males (16.4%; 95% CI, 12.2 – 21.6) than females (7.1%; 95% CI, 3.7 – 13.4). Conclusion: These results indicate the need for a vaccination program in Jazan Province and for public awareness campaign activities to combat and eradicate the disease. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.