Abstract: Human Brucellosis is one of the highly reported zoonotic diseases in the world. In Saudi Arabia, it is a highly reported zoonotic disease. Human immune response to Brucellosis is controversial. The relation of antibody titers to cytokines and CD markers of cells subpopulations was seen important to reveal the immunopathological changes at different stages of Brucellosis. The level of the cytokines, IL-1β, IL-2, IL-4, IL-8, IL-12, INF-γ and TNF-α and the CD markers, CD4+, CD8+, CD19+, NK/CD18+, MHC-II and γδ TCR were monitored 32 patients with serum titres 1/80, 1/160, 1/320 and 1/640 (8 samples/each patient). The level of the cytokines IL-2, IL-4, IL-12, INF-γ and TNF-α were decreased significantly in all serum titres. However, the CD markers CD8+, NK/CD18+ and γδ TCR as well as MHC-II increased significantly in the patients with 1/320 titer, Whereas CD19+ cells decreased significantly. The significant decrease of IL-2, IL-4, IL-12, INF-γ and TNF-α even in the titres 1/80 and 1/160 implies that organism could inflicts major defects on the resistance to human Brucellosis. However, increased expression of CD markers, CD8+, NK/CD18+ and γδ TCR could refer to the nonspecific polyclonal activation during acute Brucellosis. The dichotomy of the Th1/Th2 type cytokines activity was not observed.