The study was conducted to investigate the effects of different oils on growth performance and immune responses of chickens after challenge with lipopolysaccharide (LPS). A total of 288 chickens were assigned in a 2 × 2 factorial design. Factors were dietary fat type (4.5% maize oil or 4.5% fish oil) and immunological challenge (LPS or saline). At 20 days and 27 days of age, chickens were injected intraperitoneally with either 1 mg/kg body weight of LPS or sterile saline. LPS decreased feed intake from 21 days to 28 days of age and body-weight gain from 21 days to 42 days of age. Fish oil improved feed-conversion efficiency of chickens after LPS challenge for the first time. Fish oil supplementation decreased lymphocyte proliferation (21 days: P < 0.0001; 28 days: P < 0.0001) and the ratio of CD3+CD4+/CD3+CD8+ (21 days: P = 0.0479; 28 days: P = 0.0009) after LPS challenge. LPS challenge increased the levels of interleukin-1 (IL-1) (21 days: P < 0.0001; 28 days: P = 0.0030), IL-6 (21 days: P < 0.0001; 28 days: P = 0.0001) and tumor necrosis factor-α (TNF-α) (21 days: P = 0.0008; 28 days: P = 0.0018). And fish oil alleviated the elevations in the production of IL-6 (21 days: P = 0.0359; 28 days: P = 0.0302) and TNF-α (21 days: P = 0.0055; 28 days: P = 0.0391) induced by the LPS challenge. Fish oil alleviated the mRNA abundance elevation of nuclear factor kappa B (NFκB) (21 days: P = 0.0079; 28 days: P = 0.0017) after LPS challenge. These results showed that fish oil acts as an anti-inflammatory agent, which may be associated with down-regulation of the activated immune system. The results of pro-inflammatory cytokines and mRNA abundance results suggested that fish oil might alleviate the elevation of IL-6 and TNF-α induced by LPS through down-regulating NFκB expression.