The present study investigated the effects of dietary caffeic acid on haematological, serum biochemical, nonspecific immune and liver gene expression responses of Nile tilapia, Oreochromis niloticus. Five experimental groups of fish with mean weights of 89.85 +/- 2.5 g were used in the study; three of them were fed with caffeic acid incorporated diets (1 g kg(-1)-Cafl, 5 g kg(-1)-Caf5, 10 g kg(-1)-Caf10), whereas an additive free basal diet served as the control. Additionally, the fifth group was an antibiotic medicated diet (0.02 g kg(-1)-AMF), prepared with the florfenicol. Dietary caffeic acid especially at 5 g kg(-1) significantly increased phagocytic index, potential killing activity, respiratory burst activity, serum myeloperoxidase activity and serum catalase activity. Furthermore, increased levels of immune expression [heat shock protein 70 (HSP70), interleukin 1, beta (IL-1 beta), tumor necrosis factor (TNF-alpha), CC-chemokine (CC1), interleukin 8 (IL-8), toll-like receptor 7 (tlr-7), interferon gamma (IFN-gamma) and immunoglobulin M (IgM)] and antioxidant related genes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] in the liver of fish fed with 5 g kg(-1) caffeic acid. At the end of the 20-day challenge period the survival rates were significantly higher in the Caf5 and AMF groups compared to all other treatment groups.