We determined the incidence and clinical manifestations of human brucellosis from patients who attended a referral hospital in South of Saudi Arabia. A record-based retrospective study was conducted from January 2015 to December 2019 at King Abdulla Hospital, Bisha, Saudi Arabia. Information on patients? demographic characteristics, detailed records of signs and symptoms, and the laboratory findings were reviewed. Of 6,586 patients included, 15.8% (n 5 1,041) were infected with brucellosis. The age of infected individuals ranged from five to 95 years, with an average of 35.1 +- 21.2 years. Most infected patients were male (72.3%). Young adults (26-44 years) were the most common age group with the disease (34.1%). The annual rate of infection significantly decreased (P < 0.0001) from 33.2% in 2015 to 12.5% in 2019. An escalating number of brucellosis cases was seen in the spring and peaked during the summer. Fever (35.3%), joint pain (25.5%), generalized body ache (10.7%), and neurological symptoms (10.0%) were the most frequent clinical manifestation associated with brucellosis. Joint pain was commonly found among children (44.4%). Neurological findings were more frequent among adult patients. The study concluded that brucellosis is endemic in Southern Saudi Arabia and needs local health authority to implement preventive and educational program measures. Infected patients may present with diverse, nonspecific clinical manifestations that require intuition from clinicians to detect the disease.  Kulcsszavak: human brucellosis, clinical findings, Southern region, Saudi Arabia