Long-chain PUFA (LCP) deficiency is a frequent complication in cholestatic infants. We investigated the effects of LCP-supplemented formula on EFA status in infants with cholestasis. Twenty-three infants with cholestasis (biliary atresia after surgery, 8; intrahepatic cholestasis, 15) aged 1.9 to 4.9 mon (median 3.1 mon) were randomized to receive commercial infant formulas either without LCP or with LCP from egg phospholipids for 1 mon. Liver tests, nutrient intakes, and plasma phospholipid FA (%w/w) were determined at baseline and after intervention. At baseline, patients had high serum direct bilirubin levels (5.9 +/- 3.0 mg/dL; mean +/- SD), they were malnourished (body fat mass: 40 +/- 13% of normal) and presented with PUFA deficiency [plasma phospholipid PUFA: 28.43%w/w (26.56-30.53) in patients vs. 37.02%w/w (34.53-39.58) in controls; median (1st-3rd quartile)] with elevated Mead acid and palmitoleic acid. LCP-supplemented (n = 11) and -nonsupplemented groups (n = 12) did not differ in age, indicators of liver function, and EFA status at baseline. After the intervention, LCP-supplemented infants had higher levels of arachidonic acid [7.2 (5.9-8.8) vs. 4.2 (3.0-5.3) %w/w; P < 0.001] and DHA [2.8 (2.2-3.2) vs. 1.6 (1.0-2.1) %w/w; P < 0.05], accompanied by increased TBARS concentration: 1.9 (1.4-2.2) vs. 1.3 (1.1-1.6) nmol/mL; P < 0.05]. We concluded that LCP-supplemented formulae improve LCP status of infants with severe cholestasis but may enhance lipid peroxidation.