Objectives: Cardiac surgery induces a systemic inflammatory reaction that has been associated with postoperative mortality and morbidity. Many studies have characterized this reaction through laboratory biomarkers while clinical studies generally are lacking. This study aimed to assess the incidence of postoperative systemic inflammation after cardiac surgery, and the association of postoperative systemic inflammation with preoperative patients’ characteristics and postoperative outcomes. Design: Retrospective analysis of prospectively collected data. Analysis of the overall population and of propensity-matched subgroups. Setting: Cardiac surgery intensive care unit. Patients: Adult patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) between June 2016 and June 2017. Interventions: Mixed cardiac surgery operations on CPB. Measurements and Main Results: During the study period, 502 patients underwent cardiac surgery with CPB. One hundred forty-two patients (28.3%) fulfilled SIRS criteria at 24 hours. After performing a multivariate analysis to adjust for the procedure type and preoperative systemic inflammatory reaction syndrome (SIRS) parameters, the occurrence of SIRS was associated inversely with age and extracardiac arteriopathy, and it was associated positively with preoperative white blood cell count. Vasopressors were used more frequently in SIRS patients who further experienced longer mechanical ventilation time and length of stay in the intensive care unit (ICU). The incidence of a composite outcome including death, transient ischemic attack/stroke, renal replacement therapy, bleeding, postoperative intra-aortic balloon pump insertion, and a length of stay in ICU >96 hours was more frequent in SIRS-positive patients. There was no difference between overall and matched subgroups for in-hospital mortality. Conclusion: In this retrospective study, the clinical signs of SIRS were detected in a substantial percentage of patients who underwent cardiac surgery. The postoperative SIRS criteria were associated with a more complicated postoperative course and higher postoperative morbidity.