Sepsis is a complex disorder related to dysregulation of the host response to infection and is a major health problem worldwide owing to its high mortality rates. However, the exact mechanisms causing sepsis remains unclear because of the complexity of the underlying pathways. Dysregulation of non-canonical NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation induces septic shock by promoting pyroptosis and pro-inflammatory cytokine production (e.g., interleukin-1β) via caspase-11 and Gasdermin-D. Herein, we describe a rapid, simple method for evaluation of the degree of sepsis by investigating non-canonical inflammasome activation in both in vitro and in vivo models. The method is expected to be useful for testing and screening drugs for the treatment of sepsis.