Abstract The aim of the present study was to assess the effects of dietary supplementation with Lactobacillus salivarius (LS) ATCC 11741 and lutein (LU) on immunological, antioxidant, and growth responses, and resistance against Yersinia ruckeri infection in rainbow trout (Oncorhynchus mykiss). There were seven experimental diets containing un-supplemented diet (CTL), L. salivarius at 1 × 106 (LS6) and 1 × 108 (LS8) CFU/g, lutein at 50 (LU50) and 150 (LU150) mg/kg, L. salivarius at 1 × 106 CFU/g plus lutein at 50 g/kg (LS6+LU50), and L. salivarius at 1 × 108 CFU/g plus lutein at 150 g/kg (LS8+LU150). These diets were provided to the fish (N= 735; 14.0±0.38 g). After 60 days of feeding, all experimental treatments exhibited significantly higher growth performance, compared to the CTL treatment. The intestinal protease activity and the intestinal lactic acid bacteria population in the probiotic-treated fish were significantly higher than in the CTL fish. The intestinal lipase activity was only higher in the LS6+LU50 treatment, compared to the CTL treatment. Compared to the CTL treatment, the intestinal total bacterial count, and serum superoxide dismutase significantly increased in the LS6+LU50 and LS8+LU150 treatments. The serum catalase significantly increased in LU150, LS6+LU50, and LS8+LU150 treatments, and serum glutathione peroxidase significantly increased in the lutein-treated fish. All experimental treatments, particularly LS6+LU50 and LS8+LU150, had significantly lower serum malondialdehyde levels, compared to the CTL treatment. The levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase in LU50, LS6+LU50, and LS8+LU150 treatments were significantly lower than the CTL. All experimental treatments showed significantly higher serum lysozyme (LYZ), complement, blood respiratory burst activity (RB), and skin mucus alkaline phosphatase (ALP), compared to the CTL treatment. The highest serum LYZ, C4, total immunoglobulin (Ig), blood RB activity, and skin mucus peroxidase, ALP, and Ig were observed in the LS6+LU50 and LS8+LU150 treatments. All the experimental treatments, especially LS6+LU50, exhibited significantly lower mortality after the bacterial challenge compared to the CTL. In conclusion, dietary supplementation with 1 × 106 CFU/g L. salivarius and 50 mg/kg lutein can maximally improve growth performance, digestive enzymes, antioxidant parameters, immune responses, intestinal lactic acid bacteria, and resistance against yersiniosis in rainbow trout.