The objectives of this study were to identify protein biomarkers that would be used to guide brucellosis treatment selection, as well as to identify protein biomarkers that could be used to monitor treatment. To accomplish these goals, 191 serum samples derived from 108 patients diagnosed with un-complicated brucellosis were analyzed by proteomics. Targeted sequencing of the differentially expressed peptides between responders and non-responders resulted in the identification of 53 candidate biomarkers. Forty eight (48) proteins were selected for MRM qualifcation. Thirty five (35) of the 48 candidate protein biomarkers were qualified as differentially expressed.