Campylobacter jejuni is the leading cause of bacterial gastroenteritis worldwide, with an estimated 1.5 million human infections occurring annually in the United States alone. With chickens being considered the primary reservoir and source of infection in humans, developing effective vaccination strategies is crucial for preventing Campylobacter transmission to humans. This study aimed to examine the immunogenicity and protective efficacy of a multi-antigen subunit vaccine, consisting of C. jejuni outer membrane proteins (OMPs) and cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODN), in layer breeders and its potential to enhance the levels of C. jejuni-specific maternal antibodies in their offspring. Four groups of layer breeders were subcutaneously vaccinated with 200 μg C. jejuni OMPs and 50 μg CpG-ODN, individually or combined, or with PBS as a negative control. C. jejuni shedding and antibody levels were monitored in breeders for up to ten weeks post-vaccination. At the peak of antibody levels (the fourth week post-primary vaccination), fertilized eggs were collected and incubated in a sensitized egg incubator until hatching. Maternally derived antibodies (MDA) were measured in the serum of hatched chicks for five weeks post-hatch. The results revealed that breeders vaccinated with the combination of C. jejuni OMPs and CpG ODN exhibited a significant reduction in C. jejuni shedding by up to 1.37 log. This group also showed significantly higher serum and egg yolk IgY and IgM levels compared to the non-vaccinated negative control group, and notably, their chicks maintained significantly higher serum IgY, IgM, and IgA levels for five weeks post-hatch compared to the negative control group. Overall, these outcomes suggest that a combination of C. jejuni OMPs and CpG ODN could offer a promising vaccine strategy to reduce Campylobacter colonization in breeders and to boost and sustain high levels of C. jejuni-specific MDA in hatched chicks. Further research is needed to evaluate the protective effects of vaccine-associated MDA against Campylobacter infection in a commercial broiler model.