Pectin oligosaccharides (POS) are pectin-derived prebiotics that exerts anti-inflammatory effects on the host and stimulates an innate immune response. The role of POS in protective immunity against viral infections is not very obvious. Therefore, the prophylactic effect of POS in the mouse model induced by Poly I: C mimicking viral infection was examined. Mice fed POS showed a significant (p ≤ .05) increase in IgG, sIgA, IgA, IL-12, and a significant (p ≤ .05) decrease in the concentration of pro-inflammatory cytokines IL-5, IL-6, IL-13 and IL-17 in lung and blood serum after Poly I: C stimulation. However, the control group could not inhibit pro-inflammatory cytokines. POS also promoted the growth of the Lactobacillus, Prevotella, Rilenellaceae, and Lachanospiraceae groups. Therefore, this study demonstrate that POS has the potiential to protect against viral inflammation by altering gut microbiota and activating mucosal immunity. PRACTICAL APPLICATIONS: POS is 2-10 mer oligomers of pectin. The human gastrointestinal tract lacks the enzyme to break down POS. They are fermented by gut bacteria in the colon and stimulate the proliferation of specific gut bacteria that are positively correlated with the production of anti-inflammatory cytokines and SCFA. POS also stimulates the secretion of IgA, which inhibits bacterial and viral adhesion and protects the host. Therefore, POS can be used as a functional food ingredient in food to stimulate a specific group of gut bacteria and enhance preventive immunity.