Objective To study the anti-arrhythmic and anti-oxidative stress effects of n-3 polyunsaturated fatty acids (PUFAs) in a canine sterile pericarditis model. Methods A total of 20 dogs were randomly assigned to two groups: a control group (10 dogs) and a PUFAs treatment group (10 dogs), with sterile pericarditis created by open-chest operation in both groups. PUFAs was administered orally (2 g/d) 4 weeks before the operation until the end of the study. The inducibility and maintenance of atrial fibrillation (AF), atrial effective refractory period (AERPs), and intra-atrial conduction time were determined before and 2 days after the operation. And the level of 3-nitrotyrosine in the atrial tissue was determined by Western blotting analysis. Results The electrophysiology parameters were similar between the two groups. On day 2 after operation, the PUFAs group compared with the control group had a significantly lower AF inducibility ([11.0±7.4]% vs [28.0±10.3]%, P<0.001) and maintenance (median AF duration: 1 105 [655.8-1 406.5] s vs 2 516.5 [1 187-3 361] s, P<0.05), a significantly longer AERP ([133.4±4.1] ms vs [129.8±4.3] ms, P<0.05), and a significantly shorter intra-atrial conduction time ([46.6±4.4] vs [51.9±4.8] ms, P<0.05). Western blotting analysis showed that 3-nitrotyrosine level in the atrial tissue of PUFAs group was significantly lower than that of the control group (P<0.000 1). Conclusion Dietary PUFAs supplementation can reduce the risk of AF after operation, and its anti-oxidative stress effect might be one of the mechanisms.