Feeding high-fiber RS co-products increased (P = 0.004) the thyroid to body weight ratio and reduced (P < 0.05) the AID and ATTD of energy, dry matter, organic matter, crude protein (CP), neutral detergent fiber, acid detergent fiber, P, and most of the amino acids (AA) and monosaccharides. The reduction in digestibility was not associated with morphological changes in ileum or colon. The reduced AID of CP and AA coincided with a decrease (P = 0.030) in trypsin activity in the jejunum. The AID of starch was not affected by the dietary treatment, which also coincided with similar amylase and maltase activities in the jejunum. Variation in nutrient digestibility was observed among individual pigs within each dietary treatment. In conclusion, feeding high-fiber RS co-products to pigs enlarged the thyroid gland and reduced the AID and ATTD of most nutrients and energy. The reduction in digestibility was not associated with changes in intestinal morphology, but correlated with digestive enzyme activities.