Sepsis is frequently complicated by cerebral dysfunction, so-called sepsis-associated encephalopathy, which may be related to the presence of systemic inflammation. The mechanisms underlying this phenomenon remain unclear; however, a decrease in the plasma ratio between branched-chain and aromatic amino acids (Fischer’s ratio) has been speculated to play a role. This may cause a subsequent increase in the cerebral uptake of the aromatic amino acid phenylalanine, which can cause neurological symptoms. We therefore hypothesised that a decrease in Fischer’s ratio would occur along with an increased cerebral delivery and exchange of phenylalanine during a human-experimental model of systemic inflammation. Twelve healthy male volunteers aged 20-33 (median 26) years were enrolled in the study after ethical approval as well as oral and written informed consent. Volunteers underwent a four-hour intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (total dose of 0.3 ng/kg). Global cerebral blood flow (CBF) measurements were performed by means of the Kety-Schmidt technique using inhaled nitrous oxide [1], and arterio-jugular venous differences of aromatic and branched-chain amino acids were determined before and one hour after the cessation of LPS infusion, by use of high-performance liquid chromatography (HPLC). Cerebral delivery and net exchange of amino acids were then calculated by multiplying CBF with the arterial concentrations and arterio-jugular venous differences of amino acids, respectively. An increase in the circulating levels of phenylalanine (P < 0.01, paired samples t-test) with unaltered levels of branched-chain amino acids occurred after LPS infusion, thus causing a decrease in Fischer’s ratio (P < 0.01, paired-samples t-test). CBF was unaltered after LPS infusion; however, there was an increase in the cerebral delivery of phenylalanine (P < 0.05, paired-samples t-test), whereas the cerebral net exchange of phenylalanine remained unchanged (P = 0.8, paired-samples t-test). In conclusion, Fischer’s ratio declines and the circulating levels and cerebral delivery of the aromatic amino acid phenylalanine increased after LPS infusion in humans. However, this was not associated with a change in the cerebral net exchange of phenylalanine.