Little information is available on the patterns of changes and significance of plasma alpha-amino-n-butyric acid (ABA, μmol/L) in various conditions, particularly in sepsis. This study has been performed to assess the patterns of correlation among ABA, other amino acids, and other variables in a group of septic patients with various degrees of illness. More than 400 determinations of ABA, other amino acids, and simultaneously collected blood variables were obtained in 17 patients with sepsis. The distribution of ABA was characterized by the clustering of most measurements within the normal range (<41 μmol/L), with the spreading of abnormally increased values up to 151 μmol/L. Abnormal increases in ABA were related directly to alanine, serine, tyrosine, histidine, proline, threonine, glycine, glutamine, cysteine, lysine, cystathionine, leucine, valine, phenylalanine, arginine, and citrulline (r2 from 0.86 to 0.32) and related inversely to aspartate, taurine, and phosphoethanolamine (r2 from 0.62 to 0.50) (P< 0.001 for all). Furthermore, increased ABA was correlated with increasing total aminoacidemia, lactate, neutrophil concentration, creatinine, ammonia, osmolarity, glucose, and bilirubin and with decreasing AA Fischer ratio and peripheral O2 extraction (r2 from 0.87 to 0.16) (P< 0.001 for all). High ABA was also associated with low cholesterol, taurine, and platelet count, and with high 3-methylhistidine (partly anticipating the increase), high blood urea nitrogen, and pulmonary shunt (P< 0.001 for all). Finally, high ABA was related to the worsening of sepsis-related organ failure assessment score (SOFA score) and of most plasma AA clearances (P< 0.001 for all). Abnormally increased ABA may signal and partly anticipate the transition to an extreme derangement of septic metabolic patterns, characterized by the worsening of protein hypercatabolism with hyperaminoacidemia and by signs of impaired hepatic amino acid metabolism and oxidative metabolism. Increased ABA may represent an additional landmark of transition to extreme illness, compelling the need for the aggressive resolution of sepsis.