Background: The prevailing model for understanding chronic critical illness is a biphasic model, suggesting phases of acute and chronic critical conditions. A major challenge within this model is the difficulty in determining the timing of the process chronicity. It is likely that the triad of symptoms (inflammation, catabolism, and immunosuppression [ICIS]) could be associated with this particular point. We aimed to explore the impact of the symptom triad (inflammation, catabolism, immunosuppression) on the outcomes of patients hospitalized in intensive care units (ICUs). Methods: The eICU-CRD database with 200,859 ICU admissions was analyzed. Adult patients with the ICIS triad, identified by elevated CRP (>20 mg/L), reduced albumin (<30 g/L), and low lymphocyte counts (<0.8 × 109/L), were included. The cumulative risk of developing ICIS was assessed using the Nelson–Aalen estimator. Results: This retrospective cohort study included 894 patients (485 males, 54%), with 60 (6.7%) developing ICIS. The cumulative risk of ICIS by day 21 was 22.5%, with incidence peaks on days 2–3 and 10–12 after ICU admission. Patients with the ICIS triad had a 2.5-fold higher mortality risk (p = 0.009) and double the likelihood of using vasopressors (p = 0.008). The triad onset day did not significantly affect mortality (p = 0.104). Patients with ICIS also experienced extended hospital (p = 0.041) and ICU stays (p < 0.001). Conclusions: The symptom triad (inflammation, catabolism, immunosuppression) during hospitalization increases mortality risk by 2.5 times (p = 0.009) and reflects the chronicity of the critical condition. Identifying two incidence peaks allows the proposal of a new Tri-steps model of chronic critical illness with acute, extended, and chronic phases.