In an experimental endotoxemia model utilizing mice, serum testosterone was found to be decreased 90% two h post ip injection of 200 micrograms of lipopolysaccharide (LPS). This decrease was sustained for 9 days. The early depression of serum testosterone was shown to be associated with a decrease in Steroidogenic Acute Regulatory (StAR) protein levels while the prolonged decrease corresponded to decreased protein and transcript levels of steroidogenic enzymes in Leydig cells. This acute and prolonged depression of testosterone production could lead to impaired spermatogenesis, accessory duct failure, and contribute to decreased male fertility following acute inflammation.