HLA-DR expression on peripheral blood monocytes is reduced after cardiac surgery. Little is known about the reconstitution of HLA-DR expression on peripheral blood monocytes in patients suffering from early non-fatal perioperative complications. We conducted a prospective study to prove whether these complications adversely affect the recovery of HLA-DR expression. Before surgery (d0), on the first (d1), third (d3), fifth (5th) postoperative days, blood samples were collected from 90 patients who underwent elective cardiac surgery with cardiopulmonary bypass (CPB). HLA-DR expression was analysed flow cytometrically. Eleven patients experienced postoperative complications [mechanical ventilation of 24-48 h (n=6); reinstitution of CPB (n=2) intraoperatively; laparotomy (n=1), re-thoracotomy (n=1), re-intubation (n=1) within the first 24 h after surgery]. All patients showed a reduced HLA-DR expression after surgery with nadirs at d1 and d3. Whereas the values increased from d3 to d5 in patients with an uneventful clinical course, HLA-DR expression remained suppressed in patients with complications. HLA-DR expression is reduced after cardiac surgery with CPB. A delayed recovery of HLA-DR expression is seen in patients with early perioperative complications. These non-fatal complications appear to represent a 'second hit' resulting in a prolonged deficiency of the innate immune system. This might predispose to further infectious and septic complications.