OBJECTIVES/GOALS: Many older sepsis survivors develop chronic critical illness (CCI) with poor outcomes. Sepsis is caused by a dysregulated immune response and biomarkers reflecting PICS. The purpose was to compare serial PICS biomarkers in a) older (versus young) adults and b) older CCI (versus older RAP) patients to gain insight into underlying pathobiology of CCI. METHODS/STUDY POPULATION: Prospective longitudinal study with young (≤ 45 years) and older (≥ 65 years) septic adults who were characterized by a) baseline predisposition, b) hospital outcomes, c) serial SOFA organ dysfunction scores over 14 days, d) Zubrod Performance status at three, six and 12-month follow-up and e) mortality over 12 months. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS. RESULTS/ANTICIPATED RESULTS: Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status and mortality over 12 months. Additionally, older (versus young) and older CCI (versus older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism and anti-angiogenesis over 14 days after sepsis. DISCUSSION/SIGNIFICANCE: Older (versus young) and older CCI (versus older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS. The population of older sepsis survivors is need of interventions to lower systemic inflammation and stimulate anabolism to prevent skeletal muscle wasting and disability.