e cultures for Gram-positive bacteria, and the contribution of these bacteria to sepsis has been steadily increasing since 1979[@b2][@b3]. The clinical manifestation of sepsis is highly variable and influenced by several factors, including the health and immune status of the patient and the infectious agent involved. In the ICUs, where sepsis is a common occurrence following surgery, attention needs to be directed to the hospital-specific attributes, including (but not limited to) altered metabolism and immune-modulation due to opioid administration, to gain mechanistic insights into poly-microbial sepsis and its potential remedy[@b4][@b5].

Due to their analgesic and sedative properties, opioids are widely used in ICUs to optimize patient comfort and facilitate mechanical ventilation[@b6]. The immunosuppressive effects of opioids are well documented[@b5] and raise safety issues, especially in ICU patients. In humans, higher circulating morphine levels are observed in patients with sepsis, severe sepsis, and septic shock[@b7], and several murine sepsis models show that morphine treatment induces bacterial translocation from the gut lumen into the peritoneal organs and circulatory system[@b8][@b9]. We have previously shown that morphine accelerates the progression of LPS-induced sepsis by modulating Toll-like receptor (TLR) pathways and altering endotoxin tolerance[@b10]. However, the exact mechanisms by which opioids modulate sepsis progression remain largely elusive. In the present study, we used cecal ligation and puncture (CLP), a well-established model for inducing poly-microbial sepsis, in C57BL/6J mice treated with either opioids or placebo. The survival rates of mice were analyzed to investigate the effects of opioids on sepsis progression. We demonstrated that both morphine and methadone treatment resulted in high mortality following CLP when compared with placebo-treated animals. Furthermore, morphine promoted bacterial dissemination and increased production of the pro-inflammatory cytokine interleukin-1