Corynebacterium pseudotuberculosis is a bacillus that causes caseous lymphadenitis in small ruminants, leading to great losses to rural producers; thus, an efficient diagnosis is necessary for using disease control measures. This study aimed to evaluate the antigenic potential of four C. pseudotuberculosis recombinant proteins (rSodC, rPknG, rNanH, and rSpaC) against sera of goat and sheep experimentally infected with one of three different C. pseudotuberculosis strains. Goats were infected with CAP76 or CAP21 strain (n = 10), sheep with VD57 strain (n = 6), and a group of not-infected animals (goats and sheep) were kept as a healthy control (healthy n = 12). Sera were collected at 0, 14, 60, 90, 180, or 190days after inoculation for antigenicity testing using Western blotting and enzyme-linked immunosorbent assay (ELISA) techniques. Cross-reactivity tests with recombinant proteins were performed in goat serum experimentally vaccinated with Nocardia sp. or Rhodococcus equi bacterin. The rSodC protein showed discriminatory antigenic reactivity with a statistically significant difference against three different C. pseudotuberculosis strains evaluated in goats and sheep samples, while rPknG showed statistical significance only against two C. pseudotuberculosis strains evaluated in goats. rSodC was proved to be a strong candidate as a tool for diagnosis of C. pseudotuberculosis infection, once it was able to recognize antibodies against all strains evaluated in goats and sheep.