Leyton Orient winger Dean Cox will be out for six months after damaging the cruciate ligament in his right knee.
The 28-year-old, who has scored five goals in 16 appearances for the O's this season, suffered the injury in training last week.
"He was running with the ball and looked like he got his foot stuck in the ground," manager Ian Hendon told BBC Radio London.
"We are devastated for him and it is a massive loss for us."
Cox joined Orient in summer 2010 after leaving Brighton and has played 270 games for the east London club, scoring 58 goals.
"Paul McCallum did a similar injury and now we've lost Dean," Hendon added.
"It is not anything we have done or an impact injury. They are accidents and they happen in football."
Orient lost 3-1 at Hartlepool on Sunday, a defeat which left them seventh in League Two.
The Matchroom Stadium outfit were the early-season pace setters in the fourth tier but have slipped down the table after winning just two of their last 12 league games.
"I get judged on results, not performances," Hendon said.
"We are in and around it but we need to start winning games if we are going to be challenging this year. The results have to pick up quickly."