This study evaluated whether oyster crude polysaccharides (OPS) attenuates lipopolysaccharide (LPS)-induced immune stress in weanling piglets. Thirty healthy crossbred piglets (28 ± 1 days old) were randomly divided into five groups (6 piglets/group). Blank control and LPS groups were fed with the basal diet, while low, medium and high dose of OPS groups were fed with the basal diet supplemented with 0.5, 0.8 and 1.2 % OPS, respectively, for 30 days. LPS group, as well as low, medium and high dose of OPS groups were then injected intraperitoneally with LPS (100 μg/kg body weight), whereas the blank control group was given phosphate buffered saline. The concentrations of TNF-α, IL-1β and IL-6 in plasma were detected by ELISA. The mRNA levels of PPARγ in liver, spleen, adrenal gland and thymus were evaluated by quantitative real-time PCR. The results showed that compared with the blank control, LPS treatment significantly increased plasma IL-1β, IL-6 and TNF-α levels, which was significantly attenuated by supplementing 0.5, 0.8 or 1.2 % OPS in the diet. In addition, LPS significantly induced expression of PPARγ mRNA in liver, spleen, adrenal gland, and thymus, which was blocked by adding OPS regardless of the doses. These results indicate that dietary supplementation of OPS was able to alleviate the immune stress induced by LPS.