Excessive or inappropriate inflammation and immunosuppression are components of the response to surgery, trauma, injury and infection in some individuals and can lead, progressively, to sepsis and septic shock. The hyperinflammation is characterised by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids and other inflammatory mediators, while the immunosuppression is characterised by impairment of antigen presentation and of T-helper lymphocyte type-1 responses. Long-chain n-3 fatty acids from fish oil decrease the production of inflammatory cytokines and eicosanoids. They act both directly (by replacing arachidonic acid as an eicosanoid substrate and by inhibiting arachidonic acid metabolism) and indirectly (by altering the expression of inflammatory genes through effects on transcription factor activation). Thus, long-chain n-3 fatty acids are potentially useful anti-inflammatory agents and may be of benefit in patients at risk of hyperinflammation and sepsis. As a consequence, an emerging application for n-3 fatty acids, in which they may be added to parenteral (or enteral) formulas, is in surgical or critically-ill patients. Parenteral nutrition that includes n-3 fatty acids appears to preserve immune function better than standard formulas and appears to diminish the extent of the inflammatory response. Studies to date are suggestive of clinical benefits from these approaches, especially in patients post surgery, although evidence of clinical benefit in patients with sepsis is emerging.