Fucoidan is a sulfated polysaccharide derived from brown algae that has been reported to perform multiple biological activities, including immunostimulation. In this study, we investigated whether fucoidan has beneficial effects on endotoxemia induced by LPS, a septic model in mice. The focus of this study was on survival rates and spleen function of the mice upon treatment. We found that fucoidan had prophylactic effects on the survival rate of mice with endotoxemia. Flow cytometric analysis using antibodies for subset-specific markers revealed that fucoidan profoundly reversed the depleted population of dendritic cells in mice with endotoxemia. According to Western blot analysis, the spleen cells of LPS/fucoidan-treated mice showed a higher expression of anti-apoptotic molecules compared to those of LPS-treated mice. Also, fucoidan-treated spleen cells were more responsive to mitogens. Taken together, these results demonstrate that fucoidan pre-treatment has beneficial effects on the survival rate and function of the spleen in mice with endotoxemia. This study may broaden the use of fucoidan in clinical fields, especially endotoxemia.