The cooling system is on one of the station's solar arrays that provide electricity to the orbital outpost.
The crew spotted a steady stream of small, white frozen ammonia flakes floating away from a coolant line outside the station on Thursday, according to Nasa.
Mission managers reviewed images and data before deciding to send American astronauts Chris Cassidy and Tom Marshburn out on Saturday morning to try to stop the leak by replacing a pump on the cooling system.
"The crew is not in danger, and the station continues to operate normally otherwise," Nasa said in a statement.
Ammonia is used to cool the power systems that operate each of the station's eight solar arrays. The leak is on the far left side of the station's truss structure, in an ammonia loop that astronauts previously tried to troubleshoot during a spacewalk in November 2012.
While Cassidy and Marshburn are working outside the space station, crew commander Chris Hadfield, a Canadian astronaut, will choreograph their movements from inside the orbital outpost. Russia's cosmonauts Pavel Vinogradov, Alexander Misurkin and Roman Romanenko make up the rest of the crew.
Work was under way to reroute the remaining power channels to maintain full operation of the systems normally controlled by the solar array that is cooled by the leaking loop.
The space station, a $100-billion research laboratory that orbits 400km above Earth, is owned by the United States and Russia in partnership with Europe, Japan and Canada.
The spacewalk was being live-streamed on Nasa TV. – Reuters