Objective To investigate the alterations of soluble molecule programmed death 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1), as well as related Th1 cytokines IFN-γ and Th2 cytokines IL-4 in patients infected with Brucella. Methods The study enrolled 56 patients infected with Brucella and 48 healthy controls. Serum sPD-1 and sPD-L1 were detected by ELISA and the levels of Th1/Th2 cytokines were measured with cytometric bead array (CBA). Among them, 37 patients received follow-up. Results Compared with the control group, the serum levels of sPD-1/sPD-L1 and IL-4 increased significantly, while the level of IFN-γ decreased significantly. In the 37 patients receiving follow-up after treatment, serum levels of sPD-1/sPD-L1 and IL-4 were remarkably lower than those in pretherapy, while the level of IFN-γ was obviously higher than that in pretherapy. Conclusion The increase of sPD-1 and sPD-L1 may be involved in the process of Brucella infection.