The guides were assisting an 11-member team on the 8,481-metre (27,825-feet) tall Makalu peak, the fifth-highest mountain in the world.
Parsuram Karki of the Thamserku Expedition tour agency said the two men had complained of altitude sickness on Tuesday night at Camp II, located at 6,700 metres, but died as their team members were taking them down.
"Their bodies have been brought to the base camp," Karki told AFP.
Altitude sickness strikes when people ascend heights too quickly, with the decreased atmosphere pressure causing headaches, fatigue and dizziness.
Every year hundreds of people from around the world travel to the Himalayas in Nepal for the brief spring climbing season, when conditions are at their best.
Mountaineering is a major revenue-earner for impoverished Nepal, home to eight of the world's 14 peaks over 8,000 metres.
