AbstractImmune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim‐3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim‐3 (sTim‐3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim‐3 and human leukocyte antigen‐DR (HLA‐DR) on the circulating monocytes were detected using flow cytometry. Plasma sTim‐3 was detected by enzyme‐linked immunosorbent assay. Inflammatory factors and two kinds of A disintegrin and metalloprotease (ADAM) – ADAM10 and ADAM17 were assessed. The Tim‐3 and HLA‐DR on the monocytes decreased with increasing sepsis severity. The sTim‐3 was reduced in the sepsis and severe sepsis patients but was elevated in the septic shock patients who exhibited significant immunosuppression as predicted by HLA‐DR. sTim‐3 levels were negatively correlated with IL‐12 and TNF‐α. ADAM10 and ADAM17, sheddases of Tim‐3, exhibited trends toward elevations in the septic shock group. In conclusion, sTim‐3 was involved in the development of sepsis. The homeostasis‐promoting role of the Tim‐3 on the monocytes was disrupted, while the inhibitory role of sTim‐3 emerged during sepsis‐induced immunosuppression.