The aim of this study was to document the influence of hyperthermia on the pharmacokinetics of ertapenem. Two groups of Wistar rats, normothermic (n = 6) and hyperthermic (n = 8), were injected a single intravenous bolus of ertapenem (15 mg/kg of body weight). Hyperthermia-induced animals were placed in a water-bath at 47 °C and control group animals were kept in a water-bath at 25 °C to obtain a stable mean core temperature of 39.8 and 36.9 °C respectively. Hyperthermia induced significant higher plasma concentrations and exposure, whereas total apparent clearance and volume of distribution were significantly decreased. If confirmed in humans, these results will be of interest to take into account such modifications in hyperthermic clinical situations.