Septic infections in malnourished surgical patients show the highest morbidity and mortality rate. The attempt to correct postoperative immune and nutritional disorders by introducing immune-enhancing nutrition (immunonutrition) is a promising way of improving outcome, but as yet little is known about the mechanisms of correcting an extensive postoperative inflammatory response (systemic inflammatory response syndrome [SIRS]) to a massive infection using this type of nutrition. A significant role in the innate antibacterial and inflammatory response is played by Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns (PAMPs). The regulatory impact of immunonutrition on TLR expression in surgical septic patients seems to be a new research direction. In this paper special emphasis was put on clinical trials and the research results for the TLR-dependent immune response and anti-bacterial/anti-inflammatory response applying immunomodulatory nutrition with increased concentrations of glutamine and unsaturated fatty acids.