OBJECTIVE: Aggressive parenteral nutrition including amino acids is recommended for low birth weight infants to prevent energy and protein deficit. Their impact on acid-base homeostasis has not been examined. PATIENTS AND METHODS:We investigated the impact of dose and duration of parenteral amino acids, with cysteine, on acid-base parameters in 122 low birth weight infants. Premature infants <32 weeks, <1850g and receiving parenteral amino acids at 1.5g·kg -1 ·d -1 for an extended period (>24h), or 3g·kg -1 ·d -1 for a short (5h), extended (24h) or for prolonged (3-5 days) duration were included in the study. Data were obtained at age 0-3 days (n=43) or when clinically stable, age 3-5 days (n=49). Data from thirty infants matched for birth weight, and gestational age and receiving parenteral nutrition during the first five days after birth were also obtained. Acidosis was defined as pH<7.25. RESULTS:Acidosis was evident in all infants between 2 and 5 days after birth. Infants with large patent ductus arteriosus (PDA) exhibited significantly (p<0.05) lower pH early, had higher blood urea nitrogen levels (26 ± 9 vs. 18+8 mg/dl, p<0.05) and had greater weight loss (∼17% of birth weight), when compared with babies without PDA. Gestational age, weight loss and patent ductus arteriosus accounted for 65% of variance in acidosis. CONCLUSIONS:Low birth weight infants develop metabolic acidosis between 2-5 days after birth irrespective of dose and duration of parenteral amino acid administration.. Careful management of parenteral fluids and co-morbidities may lower the incidence of acidosis and promote protein accretion.Précis-The association between early parenteral amino acid administration at 1.5 and 3.0g·kg -1 ·d -1 and blood acid base status was examined in 122 low birth weight infants. The data show that all LBW infants develop metabolic acidosis independent of amino acid dose between 2-5 days after birth, which is exaggerated by associated co-morbidities.