The chronic intake of naturally multi-mycotoxin contaminated feed by broilers with or without titers of Yeast Cell Wall Extract (YCWE, a.k.a Mycosorb A+®), was investigated. Day-old male Cobb chicks (1600 birds, 64 pens, 25 birds/pen) were randomly allocated to diets of control (CON); diet containing mycotoxins (MT); CON + 0.2% YCWE; MT + 0.025% YCWE; MT + 0.05% YCWE; MT + 0.1% YCWE; MT + 0.2% YCWE; and MT + 0.4% YCWE. Growth performance, blood biochemical parameters and gut health were recorded over 42 days. Compared with CON, MT had reduced body weight (BW) and increased feed conversion ratio (FCR) on days 35 and 42 with increased duodenal crypt depth and fewer goblet cells. Furthermore, European Poultry Production Efficiency (EPEF) was reduced for MT versus CON. Feeding MT + 0.2% YCWE improved BW, lowered FCR, reduced crypt depth, increased goblet cell count and improved EPEF. Considering titration of YCWE (0 to 0.4%) during mycotoxin challenge, a cubic effect was observed for FCR with NC + 0.2% YCWE having the lowest FCR. These findings suggest that chronic consumption of multiple Fusarium mycotoxins present in common field concentrations can negatively impact broiler performance and gut health while inclusion of YCWE, particularly 0.2%, could be effective in counteracting mycotoxins.