Recent surgical nutrition includes the management of mediator to induce the stress response and immune function. N-3 polyunsaturated fatty acid (n-3 PUFA) were reported to increase the survival rate, and to improve the nutritional and immune status of septic or burned animals. N-3 PUFA also inhibited the proliferation and metastasis of cancer, and improved the cancer cachexia. N-3 PUFA decreased the production of cytokine and eicosanoid originated from n-6 PUFA, and reduced the inflammatory and stress response. Cell-mediated immunity was suppressed with the reduction of cytokine. But in the stressed state, N-3 PUFA ameliorated the stress induced immunosuppression. Alteration of transcription of cytokine mRNA, changes of membrane fluidity, and reduced expression of adhesion molecule were proposed to interpret these effects. In conclusion, n-3 PUFA can be applied for the surgical patients, especially for the critically ill patients.