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Purpose: Higher intakes of n-3 polyunsaturated fatty acids that are abundant in marine fishes have been long described as a 'good nutritional intervention' with increasing clinical benefits to cardiovascular health, inflammation, mental, and neurodegenerative diseases. The present study was designed to investigate the effect of daily fish oil (FO-10 mg EPA/kg body weight (BW) and 7 mg DHA/kg BW) intake by oral gavage associated with the antioxidant astaxanthin (ASTA-1 mg/kg BW) on the redox metabolism and the functional properties of lymphocytes from rat lymph nodes. Methods: This study was conducted by measurements of lymphocyte proliferation capacity, ROS production [superoxide (O) and hydrogen peroxide (HO)], nitric oxide (NO) generation, intracellular calcium release, oxidative damage to lipids and proteins, activities of major antioxidant enzymes, GSH/GSSG content, and cytokines release. Results: After 45 days of FO + ASTA supplementation, the proliferation capacity of activated T- and B-lymphocytes was significantly diminished followed by lower levels of O, HO and NO production, and increased activities of total/SOD, GR and GPx, and calcium release in cytosol. ASTA was able to prevent oxidative modification in cell structures through the suppression of the oxidative stress condition imposed by FO. l-selectin was increased by FO, and IL-1β was decreased only by ASTA supplementation. Conclusion: We can propose that association of ASTA with FO could be a good strategy to prevent oxidative stress induced by polyunsaturated fatty acids and also to potentiate immuno-modulatory effects of FO. [ABSTRACT FROM AUTHOR]