Background: Fish diseases are among the main challenges in the aquaculture industry. Feed additives are promising agents to control fish diseases by improving their innate immunity. Objectives: The present study was conducted to assess the effects of dietary supplementation with Cirsium arvense essential oil (CAEO) on immunological responses and disease resistance in rainbow trout, Oncorhynchus mykiss. Methods: The fish (mean weight: 31.31±0.15 g) were fed diets containing 0 (Cont), 2 (CAEO2), 4 (CAEO4) and 6 (CAEO6) mL/kg CAEO for 60 days at a daily ration of 5% of biomass (n=3), followed by an experimental infection by Yersinia ruckeri. Results: After 60 days of rearing, dietary CAEO significantly increased serum total protein, total immunoglobulin (Ig), lysozyme, alternative complement (ACH50), respiratory burst activity (measured by nitroblue tetrazolium [NBT] test), skin mucus lysozyme, protease, total Ig, and alkaline phosphatase (ALP). Dietary CAEO significantly decreased post-challenge mortality; Cont, CAEO2, CAEO4, and CAEO6 showed 100%, 58%, 68%, and 48% post-challenge mortalities, respectively. The highest total Ig, NBT, ACH50, mucus protease, and ALP, and post-challenge survival were observed in CAEO6 treatment; whereas, the highest serum total protein, mucus lysozyme, and total Ig were observed in CAEO4 and CAEO6 treatments. Serum lysozyme significantly increased in all CAEO-treated fish. Conclusion: CAEO can be used as a feed additive for the aquaculture of rainbow trout, as it improves immunity and disease resistance of the fish at a concentration of 6 mL/kg. © 2026 The Author(s);.