As dietary supplementation with beta-glucans can stimulate the innate immune response in the porcine gastrointestinal system (GIT), the aim of this study was to determine if the effects of beta-glucan supplementation extend beyond the GIT to systemic levels. Hence, the effects of dietary supplementation of beta-glucans derived from Laminara digitata, Laminara hyperborea, and Sacharomyces cerevisiae on cytokine expression in the porcine liver with or without ex vivo lipopolysaccharide (LPS) challenge were examined. No significant differences in gene expression were observed in the unchallenged liver tissue, but differences were observed in all supplementation groups in the LPS challenged tissue. Relative to the basal diet, IL-6 (P < 0.05) was less expressed in the S. cerevisiae supplementation group, IL-6 (P < 0.05) and TLR-4 (P < 0.05) were less expressed in the L. digitata supplementation group, and IL-10 (P = 0.06) and IL-1 alpha (P = 0.02) were more expressed in the L. hyperborea supplementation group. There was a similar to 3-fold increase in both IL-10 and IL-1 alpha in the liver samples of L. hyperborea relative to the L. digitata supplementation groups (P < 0.01). The results indicate that supplementation with beta-glucans from both yeast and seaweed sources have systemic effects evidenced by changes in cytokine expression in the liver in response to LPS challenge; however, the cytokines affected varied according to the source of the beta-glucan.