To determine if parenteral lipid minimization in infants results in essential fatty acid (EFA) deficiency. Prospective study of infants >30 days old and >34 weeks postmenstrual age receiving parenteral lipid minimization (<1.5 g kg-1 per day) with either soybean oil or fish oil and >90% of total nutritional intake parenterally in the 14 days before a serum EFA sample. Nonparametric tests were used for statistical analyses with significance at 0.05. Fifteen samples on soybean oil and nine on fish oil were included. Energy and macronutrient intakes and weight gain were similar between groups. Biochemical EFA deficiency occurred in 60% receiving soybean oil but none receiving fish oil (P<0.01). Average daily weight gain was 49% less in EFA deficient infants than EFA sufficient infants (P=0.02). Infants on lipid minimization with parenteral soybean oil, but not fish oil, are at high risk of biochemical EFA deficiency with slower weight gain.