AbstractThe crested ibis (Nipponia nippon) is endangered worldwide. Although a series of conservation measures have markedly increased the population size and distribution area of these birds, the high mortality of embryos and nestlings considerably decreases the survival potential of this bird species. High-throughput sequencing technology was utilized to compare whole genomes between ten samples from dead crested ibises (including six dead embryos and four dead nestlings aged 0–45 days) and 32 samples from living birds. The results indicated that the dead samples all shared the genetic background of a specific ancestral subpopulation. Furthermore, the dead individuals were less genetically diverse and suffered higher degrees of inbreeding compared with these measures in live birds. Several candidate genes (KLHL3, SETDB2, TNNT2, PKP1, AK1, and EXOSC3) associated with detrimental diseases were identified in the genomic regions that differed between the alive and dead samples, which are likely responsible for the death of embryos and nestlings. In addition, in these regions, we also found several genes involved in the protein catabolic process (UBE4A and LONP1), lipid metabolism (ACOT1), glycan biosynthesis and metabolism (HYAL1 and HYAL4), and the immune system (JAM2) that are likely to promote the normal development of embryos and nestlings. The aberrant conditions of these genes and biological processes may contribute to the death of embryos and nestlings. Our data identify congenital factors underlying the death of embryos and nestlings at the whole genome level, which may be useful toward informing more effective conservation efforts for this bird species.