Background and Objective: Brucellosis is a main transmittable zoonotic disease, which is endemic, and a common health burden in Iran. Adenosine deaminase (ADA) is an essential enzyme which is involved in purine metabolism and its role in immune system is very important. The aim of this study was to determine serum changes of ADA and C-reactive protein (CRP) levels in patients with brucellosis. Patients and Methods: The study was a case-control one on 36 patients and 36 controls. The serum level of ADA and quantitative CRP was measured in both patients and controls. We also measured the Wright, Coomb,s Wright and 2-mecapto ethanol (2ME) in two participants groups. Statistical analysis was performed using SPSS for windows Version 11.5 Results: ADA serum level in patients group showed a significant difference compared to control group (31.64±25.1 vs. 13.97±3.9, P<0.0001). Quantitative CRP level in patients group was higher than control group significantly (25 ±20.7 vs 6.9±4.4 , P,s Wright, and 2ME with serum ADA and CRP levels (P=NS). Conclusion: This finding shows the serum level of ADA and CRP are two important parameters in diagnosis, treatment of brucellosis with the considering of the clinical manifestations and other paraclinic findings. However it is advisable to perform more studies.