Neutrophil extracellular traps (NETs) sequester circulating tumor cells (CTCs) and promote metastasis. This study demonstrates that in a murine model of sepsis induced by cecal ligation and puncture (CLP), CTCs become trapped within NETs, leading to increased formation of hepatic micrometastases and gross metastatic disease. NET trapping was associated with increased metastatic burden, which was abrogated by NET inhibition with DNase or a neutrophil elastase inhibitor. These findings suggest that NETs play a role in cancer metastasis during systemic infection and identify NETs as potential therapeutic targets. The study shows that NETs, which are extracellular DNA webs released by neutrophils in response to inflammatory cues, can trap CTCs in vitro and in vivo. In the CLP model, NETs were found to deposit in microvasculature and trap CTCs, leading to increased metastatic burden. This effect was reversed by NET inhibition. In vitro, NETs were shown to trap both human and murine tumor cells, and this trapping was associated with increased tumor cell adhesion to microvasculature. Additionally, NETs were found to promote migration and invasion of human lung carcinoma cell lines in vitro. The study also demonstrates that NETs can facilitate tumor cell adhesion and subsequent metastasis in vivo. In the CLP model, tumor cell adhesion was significantly increased compared to sham surgery, and this was reversed by NET inhibition. Furthermore, NETs were shown to promote the survival and growth of tumor cells in distant organs, leading to the formation of micrometastases and gross metastases. The findings suggest that NETs play a critical role in the process of cancer metastasis during systemic infection. By sequestering CTCs, NETs may promote early adhesion of tumor cells to distant organ sites, facilitating metastatic disease progression. These results highlight the potential of NETs as a therapeutic target in cancer patients with severe postoperative infections.Neutrophil extracellular traps (NETs) sequester circulating tumor cells (CTCs) and promote metastasis. This study demonstrates that in a murine model of sepsis induced by cecal ligation and puncture (CLP), CTCs become trapped within NETs, leading to increased formation of hepatic micrometastases and gross metastatic disease. NET trapping was associated with increased metastatic burden, which was abrogated by NET inhibition with DNase or a neutrophil elastase inhibitor. These findings suggest that NETs play a role in cancer metastasis during systemic infection and identify NETs as potential therapeutic targets. The study shows that NETs, which are extracellular DNA webs released by neutrophils in response to inflammatory cues, can trap CTCs in vitro and in vivo. In the CLP model, NETs were found to deposit in microvasculature and trap CTCs, leading to increased metastatic burden. This effect was reversed by NET inhibition. In vitro, NETs were shown to trap both human and murine tumor cells, and this trapping was associated with increased tumor cell adhesion to microvasculature. Additionally, NETs were found to promote migration and invasion of human lung carcinoma cell lines in vitro. The study also demonstrates that NETs can facilitate tumor cell adhesion and subsequent metastasis in vivo. In the CLP model, tumor cell adhesion was significantly increased compared to sham surgery, and this was reversed by NET inhibition. Furthermore, NETs were shown to promote the survival and growth of tumor cells in distant organs, leading to the formation of micrometastases and gross metastases. The findings suggest that NETs play a critical role in the process of cancer metastasis during systemic infection. By sequestering CTCs, NETs may promote early adhesion of tumor cells to distant organ sites, facilitating metastatic disease progression. These results highlight the potential of NETs as a therapeutic target in cancer patients with severe postoperative infections.