Abstract:Sepsis is a life-threatening condition associated with high mortality rates in clinical settings. The subsequent immunosuppressive state is strongly correlated with adverse patient outcomes. Establishing robust animal models is therefore essential for elucidating the pathophysiological mechanisms of sepsis-induced immunosuppression and developing therapeutic interventions. However, current models are predominantly employed in sepsis hyperinflammation studies, while their utilization specifically for the immunosuppression phase remains limited. Additionally, standardized assessment criteria for immunosuppression are lacking across different investigations. Commonly employed models include cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) administration. While CLP effectively recapitulates clinical pathology, it suffers from significant outcome variability. Conversely, although LPS administration is technically straightforward, its artificial nature fails to replicate the polymicrobial pathogenesis of natural infection. Quantitative analysis of immune cell populations, cytokine profiles, and immune organ status provides reliable assessment of immunosuppression severity in animal models. By synthesizing recent literature, this review consolidates methodologies and assessment parameters for establishing sepsis immunosuppression models, while critically evaluating the strengths and limitations of each approach. This aims to establish a standardized experimental framework for future development of optimized sepsis immunosuppression models.