Oligonucleotides containing the dinucleotide CpG have an immunostimulatory effect in mammals. The CpG motif is interpreted as a signal of prokaryote invasion by the innate immune system and consequently activates defense mechanisms. The goal of this study was to investigate whether the immunostimulatory actions of CpG oligonucleotides take place in birds as well. To this end, birds were immunized with BSA and the serum antibody response was followed. A significantly higher BSA-specific response was observed in the CpG-treated group. Moreover, immunostimulatory DNA resulted in more persistent responses to immunization. After only one immunization, titers as high as in booster responses were observed in the CpG-treated birds. The effects were shown to depend on the presence of an unmethylated CpG core sequence in the DNA, because the reversal of CpG to GpC even caused a decrease in antibody response. These findings demonstrate that CpG oligonucleotides could be a valuable adjuvant for poultry vaccines.