We report on the case of a 73-year-old man, who was referred to our emergency department for confusion and dyspnea. He had been under a treatment of flucloxacillin for six weeks because of a possible methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis that was complicated by an acute late infection of a knee prosthesis. The laboratory work-up revealed a metabolic acidosis with a high anion gap. After exclusion of the other explanations, we retained a pyroglutamic metabolic acidosis due to concomitant intake of paracetamol and flucloxacillin, favoured by several risk factors. This diagnosis was confirmed by an organic acid dosage in the urine. After discontinuation of the drugs and a treatment with N-acetylcysteine, the evolution was favourable with correction of the metabolic acidosis and the confusional state.