Objective: To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection. Design: Double-blind placebo controlled randomized clinical trial. Setting: Department of medicine and medical intensive care unit in a tertiary university medical center. Patients and participants: A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo. Measurements and results: The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-α and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively). Conclusions: Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit.