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Introduction: chronic low-grade inflammation, or inflammaging, emerges as a crucial element in the aging process and is associated with cardiovascular and neurological diseases, sarcopenia, and malnutrition. Evidence suggests that omega-3 fatty acids present a potential therapeutic agent in the prevention and treatment of inflammatory diseases, mitigating oxidative stress, and improving muscle mass, attributes that are particularly relevant in the context of aging. The objective of the present study was to evaluate the effectiveness of supplementation with omega-3 fish oil in improving the immune response and oxidative stress in knockout mice for interleukin IL-10 (IL-10 -/- )., Material and Methods: female C57BL/6 wild-type (WT) and interleukin IL-10 knockout (IL-10 -/- ) mice were fed during 90 days with a standard diet (control groups), or they were fed/supplemented with 10% of the omega-3 polyunsaturated fatty acid diet (omega-3 groups). Muscle, liver, intestinal, and mesenteric lymph node tissue were collected for analysis., Results: the IL-10 -/- +O3 group showed greater weight gain compared to the WT+O3 ( p = 0.001) group. The IL-10 -/- +O3 group exhibited a higher frequency of regulatory T cells than the IL-10 -/- group ( p = 0.001). It was found that animals in the IL-10 -/- +O3 group had lower levels of steatosis when compared to the IL-10 -/- group ( p = 0.017). There was even greater vitamin E activity in the WT group compared to the IL-10 -/- +O3 group ( p = 0.001) and WT+O3 compared to IL-10 -/- +O3 ( p = 0.002), and when analyzing the marker of oxidative stress, MDA, an increase in lipid peroxidation was found in the IL-10 -/- +O3 group when compared to the IL-10 -/- group ( p = 0.03). Muscle tissue histology showed decreased muscle fibers in the IL-10 -/- +O3, IL-10 -/- , and WT+O3 groups., Conclusion: the findings show a decrease in inflammation, an increase in oxidative stress markers, and a decrease in antioxidant markers in the IL-10 -/- +O3 group, suggesting that supplementation with omega-3 fish oil might be a potential intervention for inflammaging that characterizes the aging process and age-related diseases.