To investigate the effect of Coriolus versicolor polysaccharides (CVPS) on the immune response of crucian carp (Corassius auratus gibelio), fish were fed diets containing CVPS at different concentrations including 0.5, 1.0 and 2.0 g kg−1 for 5 weeks. Other groups of fish were vaccinated by intraperitoneal injection (i.p.) against Aeromonas hydrophila with a killed bacterin at the beginning of the experiment and fed the same diets as described above. Additionally, control fish and vaccinated-only fish were fed basal diets without CVPS supplementation. The phagocytosis, lysozyme activity, complement components C3 and C4, E-C3bRR (Erythrocyte-C3b rosette rate) and E-CIRR (Erythrocyte-immune complex rosette rate) levels and circulating antibody titers in the serum were monitored. Five weeks after feeding the prescribed diet, fish were challenged with A. hydrophila and the mortalities recorded. Results showed that feeding non-vaccinated and vaccinated crucian carp with CVPS stimulated the phagocytosis of leukocytes, lysozyme, complement components C3 and C4, erythrocyte immune adherence, and circulatory antibody titers in serum in vaccinated crucian carp. Immune parameters increased to their highest levels after 3 weeks of feeding the diet containing 0.5 or 1.0 g kg−1 CVPS. These doses also resulted in the highest protection in the challenge experiment. Best survival (85%) was in the vaccinated group fed the diet containing 1.0 g kg−1 CVPS, whereas almost 80% of control fish (negative control) and 50% of vaccinated-only fish (positive control) died.