Oligodeoxynucleotides (ODNs) containing cytosine-phosphate-guanosine sequence (CpG) is considered as an immune stimulator when it is fed to animals. These synthetic molecules mount different immune responses in the animals including mice, chickens, ducks, dogs and horses. CpG ODNs induce specific antigenic immunity against co-administered vaccines and are well tolerated in healthy individuals and are capable of stimulating toll-like receptors (TLRs) such as TLR-9 to activate innate immunity. The CpG ODNs can be used as an adjuvant in different vaccines synthesised specifically for poultry diseases caused by viruses and bacteria. In chickens, CpG ODNs stimulate TLRs involved in humoral immunity. CpG ODNs have been used as mucosal vaccine adjuvants against several pathogens, including avian influenza and Newcastle disease. The CpG ODNs function to protect the chickens from Newcastle disease by producing plasma dendric cells (pDCs) which ultimately produce interferons (INFs). The inoculation of CpG ODNs along with the cationic microparticles and DNA vaccine for infectious bursal disease virus result in the influx of T cells and a reduction of antigen load. When CpG ODNs are used against avian leucosis, they result in significantly higher antibody titres. In many other vaccines e.g., infectious laryngotracheitis, infectious bronchitis, herpes, viral enteritis, Marek's disease virus, E. coli and Salmonella spp. including CpG ODNs exhibit immunostimulatory effects. In conclusion, CpG ODNs may be used as effective adjuvants in viral, bacterial and parasitic vaccines in poultry.