Despite the myriad of investigations in literature on cassava utilization in domestic chickens, its effects on the avian specific humoral immune system still remains elusive. This study investigated the effects of graded levels of fermented (F) and unfermented (UF) cassava diets on the lymphoid organs and its subsequent humoral immunological response in domestic chicks. One hundred day-old Yaffa White cockerels were randomly divided into five groups (A to E) of twenty birds each. The replacement of maize with 0%, 20%, 30%, fermented or unfermented cassava root meal was on a quantitative basis in each group fed for 5 weeks. All other ingredients remained constant. The mean body weight in different cassava treated groups (CTGs) showed no significant difference (P>0.05) compared with the control. The bursa and thymic weights showed both decrease and increase significant difference (P<0.05). There was significant decrease in the IBD antibody titers of CTGs compared with the control at week 5. Macroscopically, mild to moderate enlargement and atrophy of bursa of Fabricius, with petechiation of cortical surfaces of the thymus were observed. Microscopically, lesions such as interfollicular edema, interfollicular fibrosis, follicular atrophy, lymphofollicular hypoplasia, dystrophic epithelium, thickened splenic capsule, splenic lymphoid hypoplasia, thymic lymphoid hypoplasia, diffuse medullary thymic haemorrhages and Myoid cells proliferation were the consistent histopathological changes in all the CTGs. In conclusion, this study demonstrated that cassava inclusion feeds could cause subtle sublethal effects to the lymphoid organs of domestic chickens, and consequently lead to vaccine failure when it is administered for a long period of time. Keywords : Lymphoid organs, fermented and unfermented cassava, serology, pathology