Background The aim of this study was to compare the dynamics of two inflammatory response biomarkers pentraxin 3 (PTX3) and C-reactive protein (CRP) after cardiac surgery with particular regard to different postoperative clinical manifestation of inflammatory response. Patients and Methods In this study, 42 patients undergoing open heart surgery with the use of cardiopulmonary bypass were included and divided in two groups according to the extent of clinical manifestation of inflammatory response: Group A (n = 21)-patients with different severity of systemic inflammatory response syndrome (SIRS) and Group B (n = 21)-patients with uneventful postoperative period (no SIRS). The serum levels of PTX3 and CRP were evaluated and compared at the following time points: before and at the end of surgery, 6 hours, 1st, 3rd, and 7th day after surgery. Results The dynamics of CRP levels were comparable between both groups and showed the classical characteristics after cardiac surgery with a peak on the 3rd postoperative day (113 vs. 132 mg/L). In contrast, the dynamics of PTX3 showed an earlier increase of serum levels with the peak on the 1st postoperative day in both groups (36.3 vs. 42.7 ng/mL). Importantly, a significant difference of PTX3 levels was found on the 3rd postoperative day (31.1 vs. 7.0 ng/mL; p < 0.006) between the two groups showing significantly delayed decrease of PTX3 levels in patients with SIRS (Group A). Conclusion This study demonstrates considerably different dynamics of PTX3 levels after cardiac surgery in patients with SIRS and patients without SIRS, thus it may be indicative to start the appropriate therapy.