Clinical deterioration among hemodynamically stable sepsis patients occurs frequently, and patients with intermediate lactate levels (between 2.0 and 4.0 mmol/L) are particularly at risk for mortality. The aim of this study was to identify factors for predicting early deterioration in sepsis patients with intermediate levels of serum lactate. A retrospective cohort study of adult sepsis patients with lactate levels between 2.0 and 4.0 mmol/L was conducted in the emergency department of a tertiary care hospital between August 2008 and July 2010. The primary outcome was progression to sepsis-induced shock defined as persistent hypotension despite initial fluid challenge or a blood lactate concentration 4 mmol/L or greater within 72 hours of emergency department arrival. Among the 474 patients enrolled in the study, there were 108 cases of sepsis-induced tissue hypoperfusion (22.7%) and 48 deaths (10.1%). In a multivariate regression analysis, independent predictors for progression were hyperthermia, neutropenia, band neutrophils appearance, hyponatremia, blood urea nitrogen level, serum lactate level, and organ failure including respiratory, cardiovascular, and central nervous system. Initial Sequential Organ Failure Assessment score was also associated with progression. In patients with a Sequential Organ Failure Assessment score of 5 or greater, the predicted rate of progression to tissue hypoperfusion was 38.9%. Our study demonstrates potential risk factors, including organ failure, for progression to sepsis-induced tissue hypoperfusion in patients with intermediate levels of serum lactate. We suggest that an early aggressive treatment strategy is needed in patients with these risk factors.