To this day, the pathophysiology and risk factors of propofol infusion syndrome (PRIS) remain unknown. Moreover, there is no widely accepted definition of PRIS, even though it is a potentially fatal condition. While many suspected cases of PRIS have been reported in both pediatric and adult populations, the actual propofol plasma concentration (Cp) has never been clarified. In this clinical report, we described the first suspected PRIS case in which the propofol Cp was measured 25 min after 226 min of propofol infusion (7.2 µg/mL), which was 12 times higher than the predicted value (0.6 µg/mL). In the presented case, we observed gradually progressive uncontrollable hypercapnia and tachycardia, followed by severe lactic acidosis during surgical anesthesia based on the target-controlled infusion of propofol. Levels of liver enzymes were slightly elevated which suggests little or no liver damage though propofol is mainly metabolized by the liver. Meanwhile, renal impairment, a common secondary feature of PRIS, occurred concomitantly when hypercapnia and metabolic acidosis were manifested. In this case, low or delayed propofol clearance might have been a triggering factor causing severe lactic acidosis.