Caseous lymphadenitis (CL) is a contagious chronic bacterial disease of small ruminants of global relevance caused by Corynebacterium pseudotuberculosis (Cp). Unfortunately, little information is available on genetic resistance to this disease. The present study was conducted on the Suffolk breed kept in the Czechia. Three hundred twenty-one adult sheep (143 animals serologically positive and 178 serologically negative to Cp) belonging to four flocks were genotyped with the GGP Ovine 50K SNP array. A genome-wide scan was performed on the individual marker genotypes to identify polymorphisms associated with host susceptibility to CL. Genome coordinates for all SNP were based on the ARS-UI_Ramb_v2.0 ovine genome assembly (GenBank accession GCA_016772045.1). Genotyping data were quality-controlled using PLINK. Markers were removed from the analyses when they had a call rate below 97%, a minor allele frequency of less than 0.05, or showed a significant (P < 0.00001) deviation from Hardy-Weinberg equilibrium. The final dataset contained 28 478 SNP marker genotypes. GWAS analyses were performed for two classes of phenotype (negative, i.e., less susceptible animals to CL, and positive, i.e., more susceptible animals to CL) using the mixed linear model association (-mlma) method in the GCTA software tool. Two SNPs on chromosomes 11 and 20 approached genome-wide significance (raw P value < 5 x 10-5) and were considered to be suggestively significant. The most significant SNP was assigned to the TRIM16 gene, which is involved in the positive regulation of cytokine production. Further following, nine SNPs with raw P < 5 x 10-4 were revealed on different chromosomes. Three were located inside LCLAT1, PDE4D, and SPIDR genes encoding enzymes acting in phospholipid biosynthesis, signal transduction through T cell receptors, and DNA damage repair. These results provide a first insight into the genetic background of the immunological response to CL in sheep, but further research in larger populations is necessary. Estimating the contribution of SNP markers to genomic selection breeding strategies might enable the production of more disease-resistant animals.