Introduction The pathogenesis of postoperative delirium, its causes, and factors contributing to its development remain a subject of debate. We consider it promising to study the dynamics of lipoperoxidation, cortisol levels and amino acid metabolism in patients with postoperative delirium. Such studies will reveal diagnostic and prognostic markers.The aim was to identify differences in the dynamics of lipoperoxidation, amino acid balance and cortisol levels in patients with and without delirium.Materials and methods A total of 41 patients who underwent surgery for a femoral fracture under epidural anaesthesia were included in the study. All patients underwent a daily test, the Confused Consciousness Assessment Method. If it was positive, delirium was diagnosed; thus, two groups were identified: with postoperative delirium (n = 12) and without delirium (n = 29).Results In the preoperative delirium group, there was a relative lack of glucocorticosteroids as measured by reduced cortisol levels (pU < 0.01) and inhibition of lipid peroxidation as reduced Schiff bases (pU = 0.01). There were no significant differences in amino acid metabolism of the major amino acid pools. The intraoperative period in both groups had similar characteristics and no significant differences. In the postoperative period inhibition of lipoperoxidation in the delirium group changed into its greater activation, which was revealed by increased levels of ketodienes and conjugated trienes in isopropanol phase (pU < 0.01). There was also an increase in the aromatic pool (pU < 0.01) due to an increase in large neutral amino acids (phenialanine, pU = 0.0, tryptophan, pU = 0.02, tyrosine, pU < 0.01) and a decrease in the aliphatic pool (pU < 0.01). Cortisol levels remained significantly lower in the delirium group (pU < 0.01).Discussion The preoperative decrease in the studied indices in the delirium group may indicate initial reductive stress. In the postoperative period, patients with and without delirium differ in their metabolic activity with respect to lipoperoxidation and amino acid metabolism, and cortisol levels remain significantly lower in the delirium group.Conclusion The development of delirium is facilitated by initial reductive stress and a tolerant adaptation strategy.