The guinea pig model of tuberculosis is used extensively to assess the efficacy of novel tuberculosis vaccines. There are established parameters to determine vaccine efficacy in this model, but the science community currently lacks established biomarkers for early detection and monitoring of experimental disease in guinea pigs. To define a set of biomarkers that could be used as benchmarks for disease progression and early endpoint criteria, we assessed serum biochemical and hematology parameters in 2 groups of guinea pigs-one vaccinated with the attenuated Mycobacterium bovis vaccine strain (BCG) and one sham-vaccinated with saline-and then experimentally infected with a virulent strain of Mycobacterium tuberculosis. After infection, WBC showed the strongest differences between saline-inoculated and vaccinated animals, with more subtle changes in other serum biochemical parameters, including ALT and ALP. Therefore, this study provides a starting point for evaluating the utility of blood values as possible early endpoint criteria in the guinea pig model of tuberculosis.