<b>Background:</b> This study aimed at identifying genomic regions that underlie genetic variation of worm egg count, as an indicator trait for parasite resistance in a large population of Australian sheep, which was genotyped with the highdensity 600 K Ovine single nucleotide polymorphism array. This study included 7539 sheep from diferent locations across Australia that underwent a feld challenge with mixed gastrointestinal parasite species. Faecal samples were collected and worm egg counts for three strongyle species, i.e. <i>Teladorsagia circumcincta, Haemonchus contortus</i> and <i>Trichostrongylus colubriformis</i> were determined. Data were analysed using genome-wide association studies (GWAS) and regional heritability mapping (RHM).<br/> <b>Results:</b> Both RHM and GWAS detected a region on <i>Ovis aries</i> (OAR) chromosome 2 that was highly signifcantly associated with parasite resistance at a genome-wise false discovery rate of 5%. RHM revealed additional signifcant regions on OAR6, 18, and 24. Pathway analysis revealed 13 genes within these signifcant regions (<i>SH3RF1, HERC2, MAP3K, CYFIP1, PTPN1, BIN1, HERC3, HERC5, HERC6, IBSP, SPP1, ISG20,</i> and <i>DET1</i>), which have various roles in innate and acquired immune response mechanisms, as well as cytokine signalling. Other genes involved in haemostasis regulation and mucosal defence were also detected, which are important for protection of sheep against invading parasites.<br/> <b>Conclusions:</b> This study identifed signifcant genomic regions on OAR2, 6, 18, and 24 that are associated with parasite resistance in sheep. RHM was more powerful in detecting regions that afect parasite resistance than GWAS. Our results support the hypothesis that parasite resistance is a complex trait and is determined by a large number of genes with small efects, rather than by a few major genes with large efects.