The effects of dietary ginger on haematological parameters, antioxidant enzymes activites spleen histology  and disease resistance of Oreochromis niloticus  were investigated.  Four test diets containing different levels of ginger (0, 1, 2 and 3%) (W/W) were fed for O. niloticus fingerlings weighted (7.94± 0.26g) for 4 weeks. A positive correlation was observed between the level of ginger and haemato-biochemical parameters measured. The results revealed that blood parameters [(total leukocytic count (TLC), total erythrocytic counts, packed cell volume (PCV), haemoglobin concentration (HB) and differential leukocytic count (DLC)] and serum (total proteins, albumin and globulin) were significantly higher (p< 0.05) in ginger fed groups. Antioxidant enzymes including [Glutathione Peroxidase enzyme (GSH-px), Superoxide Dismutase (SOD)] showed significant increase (p< 0.05) in ginger treated groups in relation with control. While, Malondialdehyde (MDA) and liver function enzymes [Glutamic – oxaloacetic transaminase GOT (AST) and Glutamic – pyruvic transaminase GPT (ALT)] were significantly lower than the control groups. Spleen histological structure showed time and concentration dependant increase in melanomacrophaphage centers and hemosiderin pigments that reach the highest aggregations at 3rd week post feeding.  Challenge infection by A. hydrophila recorded highly significant protection reaching (90.2%) in 1% ginger treated groups for 4 weeks. The results suggest that ginger can be recommended as a supplement to O. niloticus feed to enhance resistance against A. hydrophila pathogen