Abstract Background Inbreeding depression refers to the decrease in mean performance due to inbreeding. Inbreeding depression is caused by an increase in homozygosity and reduced expression of (on average) favourable dominance effects. Dominance effects and allele frequencies differ across loci, and consequently inbreeding depression is expected to differ along the genome. In this study, we investigated differences in inbreeding depression across the genome of Dutch Holstein Friesian cattle, by estimating dominance effects and effects of regions of homozygosity (ROH). Methods Genotype (75 k) and phenotype data of 38,792 cows were used. For nine yield, fertility and udder health traits, GREML models were run to estimate genome-wide inbreeding depression and estimate additive, dominance and ROH variance components. For this purpose, we introduced a ROH-based relationship matrix. Additive, dominance and ROH effects per SNP were obtained through back-solving. In addition, a single SNP GWAS was performed to identify significant additive, dominance or ROH associations. Results Genome-wide inbreeding depression was observed for all yield, fertility and udder health traits. For example, a 1% increase in genome-wide homozygosity was associated with a decrease in 305-d milk yield of approximately 99 kg. For yield traits only, including dominance and ROH effects in the GREML model resulted in a better fit ( P < 0.05) than a model with only additive effects. After correcting for the effect of genome-wide homozygosity, dominance and ROH variance explained less than 1% of the phenotypic variance for all traits. Furthermore, dominance and ROH effects were distributed evenly along the genome. The most notable region with a favourable dominance effect for yield traits was on chromosome 5, but overall few regions with large favourable dominance effects and significant dominance associations were detected. No significant ROH-associations were found. Conclusions Inbreeding depression was distributed quite equally along the ...