<jats:p><jats:italic>Background</jats:italic>. Pathogenic infection in broilers has become an important issue in the development of poultry industry. Xylooligosaccharides released from xylan via xylanase and fermented polysaccharide of <jats:italic>Hericium caputmedusae</jats:italic> (FPHC) have antimicrobial potential against many pathogens. <jats:italic>Objective</jats:italic>. We aimed to explore the effects of xylanase and FPHC on pathogenic infection in the broilers (<jats:italic>Gallus gallus domesticus</jats:italic>). <jats:italic>Methods</jats:italic>. Three hundred and thirty 21-day male broilers were assigned into four groups: control group (CG, basic diet), xylanase group (XG, basic diet + xylanase), FPHC group (HG, basic diet + FPHC), and XHG group (basic diet + xylanase + FPHC). Average daily feed intake (ADFI) and daily gain (ADG) were measured. Microflora from broiler feces was analyzed using 16S rRNA sequencing. Serum tumor necrosis factor- (TNF-) <jats:italic>α</jats:italic>, interleukin-1<jats:italic>β</jats:italic> (IL-1<jats:italic>β</jats:italic>), IL-1 receptor antagonist (IL-1ra), IL-10, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) contents were detected using kits. The variables were compared using the Student <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>t</mml:mi></mml:math>-test between two groups. <jats:italic>Results</jats:italic>. Microbiological investigations showed that 75% of broilers were affected by bacterial pathogens in the CG group, most notably by coagulase-negative staphylococci. Comparatively, 15%, 26%, and 5% of broilers were affected by bacterial pathogens in the XG, HG, and XHG groups, respectively. Xylanase and FPHC treatment increased the ratio of ADG to ADFI and antioxidant capacity by increasing the levels of T-AOC, SOD, and GSH-Px and reducing the levels of MDA (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Xylanase and FPHC treatment improved anti-inflammatory capacity by increasing serum levels of IL-1ra and IL-10 and reducing the levels of IL-1<jats:italic>β</jats:italic> and TNF-<jats:italic>α</jats:italic>. On the other hand, the treatment increased probiotic concentration of <jats:italic>Bacillus licheniformis</jats:italic>, <jats:italic>Bacillus subtilis</jats:italic>, and <jats:italic>Lactobacillus plantarum</jats:italic> (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>), which were also proved in cell culture. <jats:italic>Conclusions</jats:italic>. Xylanase and FPHC ameliorate pathogen infection by increasing antioxidant and anti-inflammatory activities of broilers via the increase of probiotics.</jats:p>