Fat-soluble vitamin status was assessed in 36 infants diagnosed with cystic fibrosis by newborn screening in the Colorado Program. At the time of diagnosis of cystic fibrosis, 36% of infants were hypoalbuminemic, 21% had vitamin A deficiency, 35% had vitamin D deficiency, and 38% had vitamin E deficiency. None had vitamin K deficiency. Supplementation with pancreatic enzymes, a multiple vitamin preparation, and additional vitamin E was associated with normalization of serum albumin, retinol, and 25-hydroxyvitamin D and negative PIVKA testing at age 6 and 12 months. Several patients remained vitamin E deficient, but this was felt to be due to poor compliance. Biochemical evidence of fat-soluble vitamin deficiency is common before age 3 months in infants with CF and responds to supplementation in the first year of life.