Background/Aim: Human brucellosis is a true zoonosis. In Egypt, brucellosis is a significant health problem. It causes about 3% of acute febrile illnesses. Superoxide dismutases (SODs) are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. Hence, they represent an important antioxidant defense in nearly all cells exposed to oxidation, as occurs in acute brucellosis. The aim of this study was to assess SOD level during treatment of patients with acute brucellosis. Patients & Methods: Twenty six patients with acute brucellosis (with positive Standard tube agglutination test (SAT)), who were attending the out-patient clinic of Benha Fever Hospital, represent the study group (group I). They were cross matched with 10 healthy subjects negative for SAT test (group II). Both groups were subjected to investigations including: CBC, CRP, ESR, SAT and serum SOD level (by Enzyme Linked Immune Sorbent Assay; ELISA) that was assessed in patients before-, 3- and 6-weeks after initiation of combined therapy for acute brucellosis with Rifampicin and doxycycline. Results: Age and gender had no impact on SOD level in assessed patients, while ESR & CRP were significantly higher in the cases compared to control group. Monocytic count was significantly higher in the control group, with no statistically significant difference in total leucocytic count. The SOD level was progressively rising during the treatment (TTT) course and its level was significantly lower in cases than the control group, (37.5±18.12 ng/ml) for the control Vs {(10.5±9.09 & 23.85±5.19 ng/ml) P 0.05). Also there was a significant difference in SOD levels for cases both before and at end of TTT. In conclusion: Serum levels of SOD were significantly lower in patients with acute brucellosis before TTT, compared with control and those after- 6 weeks of continuous TTT. The activity of SOD was progressively increased as TTT continues, finally reaching that of healthy subjects.