R65.21 Severe sepsis with septic shock

Billable ICD-10-CM code, FY2026. Acts as a Major Complication or Comorbidity (MCC) as a secondary diagnosis.

Excludes1 (never code together)

• postprocedural septic shock (T81.12-)

Applies from R65.2 Severe sepsis

Applicable to

• Infection with associated acute organ dysfunction
• Sepsis with acute organ dysfunction
• Sepsis with multiple organ dysfunction
• Systemic inflammatory response syndrome due to infectious process with acute organ dysfunction

Code first

• underlying infection, such as:
• infection following a procedure (T81.4-)
• infections following infusion, transfusion and therapeutic injection (T80.2-)
• puerperal sepsis (O85)
• sepsis following complete or unspecified spontaneous abortion (O03.87)
• sepsis following ectopic and molar pregnancy (O08.82)
• sepsis following incomplete spontaneous abortion (O03.37)
• sepsis following (induced) termination of pregnancy (O04.87)
• sepsis NOS (A41.9)

Use additional code

• code to identify specific acute organ dysfunction, such as:
• acute kidney failure (N17.-)
• acute respiratory failure (J96.0-)
• critical illness myopathy (G72.81)
• critical illness polyneuropathy (G62.81)
• disseminated intravascular coagulopathy [DIC] (D65)
• encephalopathy (metabolic) (septic) (G93.41)
• hepatic failure (K72.0-)

Risk adjustment (HCC)

• CMS-HCC V28: HCC 2 — Septicemia, Sepsis, Systemic Inflammatory Response Syndrome/Shock
• CMS-HCC V22: HCC 2 — Septicemia, Sepsis, Systemic Inflammatory Response Syndrome/Shock
• ESRD V24: HCC 2

MS-DRG index

Defines the logic of DRG(s) 870-872 in MDC 18.

Approximate ICD-9-CM (GEMs)

• 785.52 Septic shock (approximate)
• 995.92 Severe sepsis (approximate)

Medicare Code Edits (MCE v43.1 (April 2026))

• Unacceptable principal diagnosis: These codes describe a circumstance which influences care but is not a current illness or injury, or capture only an underlying condition, and are unacceptable as principal diagnosis.

Code annotations containing back-references to R65.21

Back-references to R65.21

• Type 2 Excludes: R57.0 Cardiogenic shock ("septic shock (R65.21)")
• Type 1 Excludes: T79.4 Traumatic shock ("septic shock (R65.21)")

Back-references to R65.2

• Code Also: M35.81 Multisystem inflammatory syndrome ("severe sepsis (R65.2-)")
• Use Additional: O03.37 Sepsis following incomplete spontaneous abortion ("code to identify severe sepsis, if applicable (R65.2-)")
• Use Additional: O03.87 Sepsis following complete or unspecified spontaneous abortion ("code to identify severe sepsis, if applicable (R65.2-)")
• Use Additional: O04.87 Sepsis following (induced) termination of pregnancy ("code to identify severe sepsis, if applicable (R65.2-)")
• Use Additional: O07.37 Sepsis following failed attempted termination of pregnancy ("code (R65.2-) to identify severe sepsis, if applicable")
• Use Additional: O08.82 Sepsis following ectopic and molar pregnancy ("code (R65.2-) to identify severe sepsis, if applicable")
• Use Additional: O85 Puerperal sepsis ("code (R65.2-) to identify severe sepsis, if applicable")
• Use Additional: P36 Bacterial sepsis of newborn ("code(s), if applicable, to identify severe sepsis (R65.2-) and associated acute organ dysfunction(s)")
• Type 1 Excludes: R65.1 Systemic inflammatory response syndrome (SIRS) of non-infectious origin ("severe sepsis (R65.2)")
• Use Additional: T80.2 Infections following infusion, transfusion and therapeutic injection ("code (R65.2-) to identify severe sepsis, if applicable")
• Use Additional: T81.4 Infection following a procedure ("code (R65.2-) to identify severe sepsis, if applicable")

Diagnosis Index entries for R65.21

• Infection, infected, infective (opportunistic) › with › organ dysfunction (acute) › with septic shock
• Sepsis (generalized) (unspecified organism) › with › organ dysfunction (acute) (multiple) › with septic shock
• Sepsis (generalized) (unspecified organism) › severe › with septic shock
• Severe sepsis › with septic shock
• Shock › endotoxic
• Shock › gram-negative
• Shock › septic (due to severe sepsis)

Nearby codes

• R65.1 Systemic inflammatory response syndrome (SIRS) of non-infectious origin
• R65.10 Systemic inflammatory response syndrome (SIRS) of non-infectious origin without acute organ dysfunction
• R65.11 Systemic inflammatory response syndrome (SIRS) of non-infectious origin with acute organ dysfunction
• R65.2 Severe sepsis
• R65.20 Severe sepsis without septic shock
• R65.21 Severe sepsis with septic shock (this code)