Protein S deficiency patient is characterized by recurrent thrombosis, and its risk is higher intraoperatively, especially in cardiac surgery involving cardiopulmonary bypass. Two heparin cessation periods are defined in cardiac surgery. One is the period between the cessation of heparin 4 to 5 h before surgery and the heparinization prior to cardiopulmonary bypass. The other is the period between protamine administration and resumption of heparin postoperatively. Because the risk of thromboembolism is high during the period of heparin cessation, other anticoagulants are necessary. Although fresh frozen plasma, rich in protein S, is often used in cardiac surgery for protein S deficiency patients, the most appropriate times and volume of its administration to prevent thromboembolism remain poorly understood. We herein report a case of on-pump coronary artery bypass grafting in a patient with protein S deficiency who received fresh frozen plasma targeting the two heparin cessation periods. Some qualitative measurements to identify the effect of fresh frozen plasma on the protein S level are desirable to evaluate whether our present administration strategy has any beneficial effects on protein S deficiency patients.