High temperature heat pipes were proposed for space reactor cooling because of their thermal efficiency, inherent safety, and self-actuating operation. Sodium/GH4099 heat pipes were designed and fabricated in China Academy of Aerospace Aerodynamics (CAAA). And their startup properties and thermal response were investigated systematically. It was found that sodium/GH4099 heat pipes startup successfully at 950 °C heating, displaying an uniform temperature of about 800 °C. On the other hand, charging ratio affected the startup properties significantly. Startup failures occurred for heat pipes with 24% and 30% sodium charging. Under simulated space reactor environment, pre-oxidation of GH4099 surfaces could decrease axial temperature of sodium/GH4099 heat pipes greatly. With pre-oxidation of GH4099, axial temperatures of heat pipes decreased from 1138–1198 °C to 890–951 °C. These temperatures were lower than the end-use temperature of GH4099 alloy. Therefore, it was concluded that pre-oxidized sodium/GH4099 heat pipes were candidate devices for space reactor cooling.