BACKGROUND: CMV viremia is a contributor to poor outcomes in critically ill patients with sepsis. OBJECTIVES: To assess the expression levels of genes encoding inflammasome-related proteins in the development of CMV viremia in critically ill patients with sepsis. STUDY DESIGN: A cohort of CMV-seropositive critically ill patients with sepsis due to bloodstream infection underwent weekly testing for CMV viremia. Blood samples to evaluate mRNA levels of genes encoding CASP1, ASC, NLRP1, NLRP3, and NLRP12 were collected at the time of enrollment. Clinical outcomes were assessed at 30days or until death/discharge from ICU. RESULTS: CMV viremia was documented in 27.5% (8/29) of the patients, a median of 7days after the onset of bacteremia. Patients with sepsis who developed CMV viremia had higher CASP1 although this was not statistically significant (relative mean 3.6 vs 1.8, p=0.13). Development of high grade CMV viremia however, was significantly associated with CASP1; septic patients who developed high grade CMV viremia had significantly higher CASP1than all other patients (relative mean 5.5 vs 1.8, p=0.016). CONCLUSIONS: These data document possible involvement of inflammasome in the pathogenesis of CMV. Regulating the host immune response by agents that target these genes may have implications for improving CMV-related outcomes in these patients.