Abstract: Background and Objective: Campylobacter jejuni (C. jejuni) is a commensal microorganism in birds that causes diarrhea due to intestinal inflammation, which leads to feet damage from standing on wet litter. This study aimed to investigate the prevalence and virulence of C. jejuni in broiler chickens, as well as determine histopathological changes in the chicken gut following infection. Materials and Methods: A total of 200 infected broiler chicken samples (100 cecal contents, 50 livers and 50 spleens) were collected from different farms at Dakahlia Governorate in Egypt. Broilers samples were subjected to Campylobacter isolation procedures. Campylobacter jejuni isolates were distinguished from other Campylobacter spp. using the uniplex PCR-targeting mapA gene. Campylobacter jejuni isolates were also evaluated for the presence of cdtA and flaA genes. Evaluation of gut histopathological changes after C. jejuni infection was carried out in twenty day-old broiler chicks. Results: In total, sixty-eight C. jejuni isolates (18 isolates from the liver samples, 12 from spleen samples and 38 from cecal contents) were recovered with an overall prevalence rate of 34%. The flaA gene was successfully identified in all Campylobacter isolates, while cdtA, was identified in only 62 (91.17%) isolates. Several pathological changes and inflammatory responses were found in the chicken gut as a result of C. jejuni infection. Conclusion: The prevalence of flaA and cdtA revealed a high rate of adherence and cytotoxicity-associated genes. In addition, several histopathological changes were found in the chicken gut. These findings confirmed that C. jejuni infection has a significant impacton poultry health and welfare and C. jejuni is a harmful gut commensal microorganism.