Introduction: Brucellosis remains a major public health concern in Algeria, particularly in agro-pastoral regions like Sétif. This study aims to describe the clinical, epidemiological, and microbiological characteristics of human brucellosis cases managed at the University Hospital of Sétif. Methods: A retrospective descriptive study was conducted on 37 patients hospitalized at the Infectious Diseases Department between 2021 and 2024. All cases were confirmed by the isolation of Brucella spp. from blood cultures or localized samples. Statistical analysis included 95% confidence intervals (CIs) for key proportions, Fisher’s exact test for categorical variables and the Binomial test for gender distribution. A p-value < 0.05 was considered statistically significant. Results: A total of 37 patients were included. A significant male predominance was confirmed (78.4% vs. 21.6%; p = 0.001), with a mean age of 43 years (SD ± 15.6). The temporal distribution showed a peak in 2022 (32.4%), followed by a fluctuation in annual incidence without a linear trend (p > 0.05). The hallmark clinical sign was undulant fever (97%), frequently associated with arthralgia (19%) and headache (11%). Focal osteoarticular complications were identified in 10.8% of the cohort (n=4), specifically spondylodiscitis (n=2) and sacroiliitis (n=2). Notably, all complicated cases occurred in male patients; however, this association did not reach statistical significance (Fisher’s exact test, p = 0.55), likely due to the limited sample size. Conclusion: Human brucellosis in Sétif is characterized by a high burden among middle-aged men and significant osteoarticular morbidity. The lack of a declining trend over four years underlines the urgency of an integrated "One Health" surveillance system to control the animal reservoir and improve early clinical detection.