A feeding trial of 62 days was conducted to investigate the effects of dietary administration of a probiotics compound consisting of Bacillus velezensis V4 CGMCC 10149 and Rhodotorula mucilaginosa CGMCC 1013 on growth, immune response, antioxidant capability, and disease resistance of juvenile Atlantic salmon (Salmo salar L.) reared in a recirculating aquaculture system (RAS). Atlantic salmon were distributed in four equal groups, each with three replicates, which received one of the following experimental diets: Control (non-supplemented diet); T1 (B. velezensis V4 5 x 10(6) CFU g(-1), R. mucilaginosa 5 x 10(7) CFU g(-1)), T2 (B. velezensis V4 1.5 x 10(7) CFU g(-1), R. mucilaginosa 1.5 x 10(8) CFU g(-1)), and T3 (B. velezensis V4 2.5 x 10(7) CFU g(-1), R. mucilaginosa 2.5 x 10(8) CFU g(-1)). Administration of the probiotics compound had significant effects on growth performance, feed utilization, immune response, and antioxidant capability of Atlantic salmon, and mortality was significantly reduced (P < 0.05). After the feeding trial, fish were challenged with Aeromonas salmonicida (A. salmonicida) and cumulative mortality was recorded for the next 7 days. The cumulative mortality was lower in Atlantic salmon fed with the probiotics compound, especially in the T1 group, compared to the control. These results demonstrated that multi-probiotics had beneficial effects as an antibiotic replacer in terms of growth performance, non-specific immune responses and disease resistance in salmon. The present study demonstrated B. velezensis V4 and R. mucilaginosa compound as a beneficial dietary probiotics for juvenile Atlantic salmon reared in a RAS with the capability of improving growth performance and enhancing disease resistance by immunomodulation.