Cancer-related indoleamine (2, 3)-dioxygenase up-regulation by interferon-γ might influence quality of life by depleting serum tryptophan. We correlated serum tryptophan levels with immune activation and quality of life in patients with colorectal liver metastases. Venous blood was sampled from patients with primary colorectal cancer and from patients with metachronous colorectal liver metastases who completed quality of life and psychological questionnaires. Serum tryptophan, kynurenine, neopterin, interleukin 2 soluble receptor α (IL-2 sRα), soluble tumour necrosis factor receptor I (sTNF RI), interleukin 6, and C-reactive protein were measured. Liver metastasis volume was estimated by computerised tomography, and survival from blood sampling was noted. Sixty-six patients with colorectal cancer were studied (39 males; median age 66 years) of whom 25 had colorectal liver metastases only (17 males; median age 62 years; median liver metastasis volume 208 ml; median survival 234 days). Reduced serum tryptophan was significantly associated with Rotterdam Symptom Checklist physical symptom (r=− 0.51, P= 0.01) and Sickness Impact Profile (r=− 0.42, P= 0.04) scores, and correlated with increased serum neopterin (r=− 0.36, P= 0.003), IL-2 sRα (r=− 0.51, P= 0.01) and sTNF RI (r=− 0.45, P= 0.02) levels. Stepwise regression analyses suggested that serum tryptophan was an independent predictor of Rotterdam Symptom Checklist physical symptom (regression coefficient− 20.78, P= 0.01) and Sickness Impact Profile (regression coefficient− 109.09, P= 0.04) scores. The results supported a role for interferon-γ-mediated serum tryptophan decrease in cancer-induced quality of life deterioration.