This study aimed to identify loci underlying variation in parasite resistance, as measured by worm egg count (WEC), in a large multi-breed sheep population using genome-wide association studies (GWAS) and regional heritability mapping (RHM) approaches. A total of 7153 animals with both genotype data and WEC phenotypes were included in this analysis. Strong evidence of association was observed on chromosome 2 by both approaches. However, RHM had a greater power to identify loci than GWAS analysis. RHM identified an additional region at the genome-wide significance level on chromosome 6. This region was also previously found to be associated with mastitis resistance and facial eczema susceptibility in sheep, indicating that some pleiotropic effects are possibly affecting a wide range of sheep diseases. Three other regions on chromosome 1, 3 and 24 were also reached the significance threshold. However, these regions accounted for a small proportion of genetic variance, suggesting that parasite resistance is a complex disease with a large number of genes involved in the mechanism of resistance.