To determine whether preoperative inflammation predisposes to major postoperative complications (PC) and poor outcome. Prospective data collection of 153 consecutive patients aged 73+/-6 years scheduled for lung resection at a tertiary cancer center. High sensitivity C-reactive protein (CRP) and interleukin (IL)-6 levels were measured before surgery, on arrival to the postanesthesia care unit, and on the first morning after surgery. PC occurred in 9/153 (5.9%) patients. In comparison to patients without PC, those with PC had a greater history of hypertension (P=0.047), higher frequency of non-steroidal anti-inflammatory drug use (P=0.007) and had a lower preoperative albumin level, 3.75+/-0.65 g/dl versus 4.28+/-0.33 g/dl, P=0.03. Receiver operating characteristic analysis demonstrated a strong association between PC and preoperative CRP (area under the curve of 0.86), albumin (area under the curve of 0.86) and less so for IL-6 (area under the curve of 0.79). Markers of inflammation, CRP and IL-6, can help distinguish patients who are at high risk for major PC. These preliminary and novel data suggest that in addition to low albumin, a previously described marker of outcome, systemic inflammation is likely to be important in the pathogenesis of important PC.