Alterations in neopterin concentrations and tryptophan degradation accompany the activation of cellular immune systems. Accordingly, in a variety of diseases, mainly in infections, elevated neopterin levels and tryptophan degradation have been observed. This study aimed to assess serum neopterin levels and tryptophan degradation in intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS, n = 9), sepsis (n = 8), septic shock (n = 10), and multiple organ dysfunction syndrome (MODS, n = 7) at the first day of ICU hospitalization. The kynurenine-to-tryptophan (kyn/trp) ratio was used in order to evaluate the degree of tryptophan degradation. The results of each patient group were compared with the control group (n = 30). The differences among the ICU groups and the correlations between APACHE II scores and neopterin concentrations or tryptophan degradation were investigated. All patient groups presented statistically higher kyn/trp and neopterin levels than the controls. The sepsis, septic shock, and MODS group had markedly higher neopterin levels than the SIRS group (all P < 0.05). Additionally, it was found that the survivor group had significantly lower neopterin levels compared with non-survivors (P < 0.05) and lower kyn/trp, but the latter difference was not significant. Neopterin levels and kyn/trp were both correlated with APACHE II score (both P < 0.05). The results indicate that serum neopterin levels and tryptophan degradation correlate well with the severity of the disease in ICU patients, and this was true even at the first day of hospitalization in the unit.