She was selected as an Astronaut Candidate by NASA in July 2000. After two years of training and evaluation she qualified as a Mission Specialist and was assigned for technical duties in the Astronaut Office Station Operations Branch. She was Crew Support Astronaut for the Expedition 6 crew during their six-month mission on the ISS. In July 2006, Nyberg took part in , a deep-sea training and simulation exercise at the Aquarius underwater laboratory to help NASA prepare for the return of astronauts to the Moon and manned missions to Mars. Nyberg and her crewmates lived and worked underwater for seven days.