Inclusion Criteria: 

• Age > 18  years old.
• Suspected or confirmed infection as evidenced by ordering of blood cultures and administration of at least one antimicrobial agent.
• Anticipated or confirmed intensive care unit (ICU) admission.
• Acute respiratory and/or cardiovascular organ dysfunction attributed to sepsis as evidenced by at least one of the following requirements:
  • Respiratory Support Requirement – Acute hypoxemic respiratory failure defined as persistent hypoxemia (PaO2/FiO2 ≤ 300 or SpO2/FiO2 ≤ 315) requiring (1) intubation and mechanical ventilation, or (2) positive pressure ventilation via tight-fitting face mask (i.e. CPAP or BIPAP) or (3) high flow nasal cannula ≥ 40 LPM flow and FiO2 ≥ 0.40
• Vasopressor Requirement – Continuous infusion of norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine or other vasopressor agents at any dose for greater than 1 hour and required to maintain a mean arterial pressure ≥ 65 mm Hg despite intravenous crystalloid infusion of at least 1000cc.

Exclusion Criteria:

• Age < 18 years of age.
• Weight < 40 kg.
• Prior enrollment in VICTAS.
• Qualifying organ dysfunction no longer present at the time subject would be randomized (does not require either (1) respiratory support as defined above to maintain PaO2/FiO2 > 300 or SpO2/FiO2 > 315 or (2) vasopressor infusion to maintain a mean arterial pressure ≥ 65 mm Hg).
• Cardiovascular or respiratory organ failure caused by an illness other than sepsis.
• First episode of qualifying organ dysfunction during the current ED or ICU admission occurred > 24 hours before subject could be randomized (patients may be reconsidered for enrollment during a subsequent ED or ICU admission)
• Limitations of care (defined as refusal of cardiovascular and respiratory support modes described in inclusion criteria 7.1.b) including "do not intubate" (DNI) status.
• Current hospitalization > 30 days at time of randomization.
• Chronic hypoxemia requiring supplemental non-invasive oxygen (nasal cannula or NIPPV) or home mechanical ventilation.
• Chronic cardiovascular failure requiring home mechanical hemodynamic support (e.g., LVAD) or home chemical hemodynamic support (e.g., milrinone).
• Known allergy or known contraindication to vitamin C, thiamine, or corticosteroids (including previous history or active diagnosis of primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion, or known G6PD Deficiency).
• Use of vitamin C at a dose of > 1g/day (IV or oral) within the 24 hours preceding first episode of qualifying organ dysfunction during a given ED or ICU admission.
• Chronic disease/illness that, in the opinion of the site investigator, have an expected lifespan of < 30 days unrelated to current sepsis diagnosis (e.g., stage IV malignancy, neurodegenerative disease, etc.).
• Pregnancy or known active breastfeeding.
• Prisoner or Incarceration.
• Current participation in another interventional research study*.
• Inability or unwillingness of subject or legal surrogate/representative to give written informed consent.
  • *Note: Co-enrollment in other interventional research studies requires written permission from the VICTAS Executive Committee in advance of subject identification.