Wasps captain Tom Rees will be out for between six and nine months after injuring his knee in a pre-season game against Agen.
The 26-year-old flanker ruptured his anterior cruciate ligament and now looks set to miss the majority of the upcoming Premiership season.
Rees has suffered a catalogue of serious injuries and has missed much of the past two Premiership seasons.
Coach Dai Young said: "It is a huge blow for Tom and everyone at Wasps."
The former Wasps academy product, who has made 102 appearances for the side, had surgery on a shoulder injury in December 2010 having only returned to action from an 11-month lay-off in March.
Young added: "We all saw how incredibly hard Tom worked to get back to full fitness from last season's injury so this is desperately disappointing.
"As director of rugby, Tom was someone I had earmarked to have a major impact this season both on and off the pitch and he will be sorely missed. We all wish him the best in his recovery."
The England international, who has won 15 caps for his country, tore a medial knee ligament in 2008, and has suffered several problems with his right shoulder.
He was named in the 2007 World Cup squad, but despite having impressed for his country, has not appeared for England since 2008.