The impact of immune system stimulation (ISS) on the ileal nutrient digestibility and utilisation of dietary methionine plus cysteine (SAA) intake for whole-body protein deposition (PD) was evaluated in growing pigs. For this purpose, sixty barrows were used in two experiments: thirty-six pigs in Expt I and twenty-four pigs in Expt II. Pigs were feed restricted and assigned to five levels of dietary SAA allowance (three and two levels in Expt I and II, respectively) from SAA-limiting diets. Following adaptation, pigs at each dietary SAA level were injected with either increasing amounts of Escherichia coli lipopolysaccharide (ISS+; eight and six pigs per dietary SAA level in Expt I and II, respectively) or saline (ISS − ; four and six pigs in Expt I and II, respectively) while measuring the whole-body nitrogen (N) balance. After N-balance observations, pigs were euthanised, organs were removed and ileal digesta were collected for determining nutrient digestibility. Ileal digestibility of gross energy, crude protein and amino acids was not affected by ISS (P>0·20). ISS reduced PD at all levels of dietary SAA intake (P< 0·01). The linear relationship between daily dietary SAA intake and PD observed at the three lowest dietary SAA intake levels indicated that ISS increased extrapolated maintenance SAA requirements (P< 0·05), but had no effect on the partial efficiency of the utilisation of dietary SAA intake for PD (P>0·20). Physiological and metabolic changes associated with systemic ISS had no effect on the ileal digestibility of nutrients per se, but altered SAA requirements for PD in growing pigs.