The continuous rise in opioid overdoses in the United States is predominantly driven by very potent synthetic opioids, mostly fentanyl and its derivatives (fentanyls). Although naloxone (NLX) has been shown to effectively reverse overdoses by conventional opioids, there may be a need for higher or repeated doses of NLX to revert overdoses from highly potent fentanyls. Here, we used positron emission tomography (PET) to assess NLX’s dose-dependence on both its rate of displacement of [11C]carfentanil ([11C]CFN) binding and its duration of mu opioid receptor (MOR) occupancy in the male rat brain. We showed that clinically relevant doses of intravenously (IV) administered NLX (0.035mg/kg, Human Equivalent Dose(HED) 0.4mg; 0.17mg/kg, HED 2mg) rapidly displaced the specific binding of [11C]CFN in thalamus in a dose-dependent manner. Brain MOR occupancy by IV NLX was greater than 90% at 5 minutes after NLX administration for both doses, but only 50% occupancy remained at 27.3 min and at 85 min after 0.035mg/Kg and 0.17 mg/Kg NLX, respectively. This indicates that the duration of NLX occupancy at MORs is short-lived. Overall, these results show that clinically relevant doses of IV NLX can promptly displace fentanyls at brain MORs, but that repeated or higher NLX doses may be required to prevent re-narcotization following overdoses with long-acting fentanyls.