Cattle trypanosomosis caused by Trypanosoma vivax is a widely distributed disease in Africa and Latin America. It causes significant losses in the livestock industry and is characterized by fever, parasitemia, anemia, lethargy, and weight loss. In this study we evaluated the virulence (capacity to multiply inside the host) and pathogenicity (ability to produce disease and/or mortality) patterns of two T. vivax strains (TvMT1 and TvLIEM176) in experimentally-infected sheep and determined the proteins differentially expressed in the proteomes of these two strains. There was a marked difference in the virulence and pathogenicity between both T. vivax strains: TvLIEM176 showed high virulence and moderate pathogenicity, whereas TvMT1 showed low virulence and high pathogenicity. In the proteomic analysis, we identified a total of 29 proteins associated with the different biological behaviour, of which 14 exhibited significant differences in their expression level between the two strains. The proteins evidenced in this study are considered potential virulence and pathogenicity biomarkers in T. vivax infections, and deserve further investigations to precise their functional role in the host-parasite interactions.