Pseudotuberculosis, also known as caseous lymphadenitis (CLA), is an infectious disease mainly affecting sheep and goats, caused by the bacterium Corynebacterium pseudotuberculosis (Cps). The study deals with research into the genetic resistance of sheep to this disease, which can also be transmitted to humans. For the recovery of breeds, emphasis is placed on the importance of breeding for health traits, which represents a long-term and stable solution compared to vaccination and the application of antibiotics. The study’s goal was to find a relationship between the disease and the genome of animals, which would make it possible to explain the genetically determined individual susceptibility or sensitivity to the disease. During 2019-2023, an effective herd monitoring strategy was developed, and measures were introduced to limit the spread of CLA, including long-term separation of infected animals. The research included initial screening of antibodies against CLA in blood serum on more than 40 sheep and goat farms in the Czech Republic and subsequent regular monitoring of antibody levels in selected flocks using the laboratory ELISA method. The genomic association study included 321 Suffolk sheep from four farms over four years and divided into healthy, uninfected, and diseased, infected sheep. DNA genotyping was performed using the GGP Ovine 50K genomic chip. An association genomic analysis to estimate the relationship between the genome and the occurrence of CLA antibodies was performed by a mixed linear model using the GCTA program. The study revealed that average CLA absorption was 18-31% across the farms studied. Two genetic markers (SNPs) associated with the production of antibodies against Cps were identified, while the most functionally significant marker is located in the TRIM16 gene, which encodes one of the enzymes essential for cellular autophagy, i.e., the degradation of damaged cell proteins and pathogenic agents. This gene is important for the innate immune response and limits the multiplication of the Cps bacterium. The results of the pilot association study yielded valuable insights into the genetic resistance of sheep to CLA, which can be used in breeding for health traits. Identifying genetic markers has contributed to understanding the interaction between the sheep genome and the Cps pathogen, which holds promise for future breeding programs.