Important aspects of more than one multi-mycotoxin in feed, are the synergistic and additive effects which may result in negative effects on immunity and liver health of animals. The aim of the feeding trial was to investigate the effects of a multi-mycotoxin contaminated diet on immune parameters and liver health in weanling piglets. Twenty-four female weanling piglets were randomly assigned to 2 groups with 12 piglets each. Piglets were assigned to a vaccination program including hog cholera, pseudorabies and foot and mouth disease. Naturally mycotoxin contaminated corn was used to prepare the feed. Groups were as following: negative control group (A) and a mycotoxin contaminated (ZEN 1183 ppb, DON 1740 ppb, FUM 988 ppb) feed group (B). Parameters evaluated included antibody titers for pseudorabies referred to as sample to negatives ratio (S/N 0.6 was defined as positive), plasma CD4+/CD8+, IL-2, TNF-α, IgA, IgG, IgM, total plasma protein (TP) and liver enzymes (ALT, AST). The ratio of S/N in group B was significantly higher compared with group A at d 42 (P < 0.05). There were no significant differences of plasma CD4+/CD8+ among the 2 groups. The plasma IL-2 levels of group B were significantly lower than group A at d 14, 28 and 42 (P < 0.05). The plasma TNF-α level of group B was significantly lower than group A at d 28 and 42 (P < 0.05). The IgA, IgG levels of group B were significantly lower than group A at d 28 and 42 (P < 0.05). There was no significant difference of IgM among the 2 groups. Plasma TP levels of group B were significantly lower than group A at d 14, 28 and 42 (P < 0.05). Liver enzymes AST and ALT of group B were significantly higher compared with group A at d 14, 28 and 42 (P < 0.05). To conclude, the combination of mycotoxins can damage the liver and impair immune response in weanling piglets. The decreased antibody titer against pseudorabies and the increase of S/N ratio in the group fed with mycotoxin-contaminated diet, suggests animal’s decreased protection against pseudorabies when mycotoxins are present. This points to the need for greater awareness of a multiple mycotoxin contamination in feed and the protection of animals against said toxins.