Aim: To investigate the relationship between delirium and tryptophan and its metabolites in critically ill older patients. Findings: The level of TRP was significantly (borderline) decreased among patients with delirium (p = 0.056). The KYN/TRP and QA/TRP ratios were statistically and significantly higher in patients with delirium than those without (p < 0.001 and p = 0.016, respectively). The best predictive values for detecting delirium were calculated as ≤14,100 ng/mL for TRP (AUC: 0.601, p = 0.052), >1.12 for KYN/TRP ratio (AUC: 0.704, p < 0.001), and > 0.75 for QA/TRP ratio (AUC: 0.627, p = 0.013). The QA/TRP ratio showed independent and borderline significant association with being delirium in multivariable regression analysis (Odds ratio: 2.007, p = 0.066). Message: This study demonstrated that tryptophan and its metabolites obtained within the first 24 h of ICU admission might have predictive value for determining high-risk older patients for delirium.