Background. Lifespan extension is achieved through long-term application of dietary restriction (DR), and benefits of short-term dietary restriction on acute stress and inflammation have been observed. So far, the effects of short-term DR in humans are relatively unknown. We hypothesized that short-term DR in humans reduces the acute phase response following a well defined surgical trauma. Methods. Thirtylive kidneydonorswererandomized between 30% preoperative dietary restriction followed by 1 d of fasting (n = 17) or a 4 d ad libitum regimen (n = 13) prior to surgery. Leukocyte subsets and numbers and serumcytokine levelswere determined. Whole blood was stimulated with lipopolysaccharide (LPS) and cytokine production was determined. Results. A clear trend towards lower numbers of postoperative circulating leukocytes was observed in the DR group. IL-8 serum levels were significantly higher in the DR group over the first 6 postoperative d (P = 0.018). After LPS stimulation, significantly less TNF-alpha (P = 0.001) was produced by blood obtained postoperatively compared with preoperative blood from the DR group. This was not observed in the control group. Conclusions. A relatively short preoperative dietary restriction regimen was able to modify certain aspects of the postoperative acute phase response. These data warrant further studies into the dietary conditions that improve stress resistance in humans. (Dutch Trial Registry number: NTR1875). (C) 2011 Elsevier Inc. All rights reserved.