In this case report we present a singular case of metabolic acidosis seen in a 78-year-old female who was admitted to the intensive care unit (ICU) with dyspnoea, tachypnoea and tachycardia due to paracetamol and flucloxacillin usage. Laboratory examination revealed a high anion gap metabolic acidosis caused by accumulation of 5-oxoproline, otherwise known as pyroglutamic acid. Treatment consisted of discontinuation of the offending drugs and supportive care with sodium bicarbonate, inotropic medication and mechanical ventilation. Seven days after ICU admission, treatment was complicated by recurrence of metabolic acidosis after discontinuation of sodium bicarbonate. Our patient also developed 5-oxoproline-associated metabolic encephalopathy. We demonstrate that the elimination of 5-oxoproline will take longer than expected. Furthermore, this case clearly illustrates the potentially unexpected delayed clearance of 5-oxoproline. We also briefly discuss treatment modalities. © 2020, Netherlands Society of Intensive Care. All rights reserved.