Virgin Atlantic chief commercial officer Julie Southern is leaving the airline next month.
The decision comes just weeks after Southern, who has been with Virgin since 2000, lost out on the chief executive job to Craig Kreeger.
Southern was believed to be the most likely candidate to replace Steve Ridgway, who retired after 11 years.
But instead the airline recruited Kreeger from America Airlines.
A statement from Virgin said Southern was "moving on to pursue new challenges".
It added: "She leaves the airline having most recently set up the Delta joint venture deal and has been pivotal in leading the airline’s commercial endeavours during times of rapid growth and expansion. She will remain a close friend of the airline and we wish her well."
