Henry Paul will miss the remainder of the season after Gloucester's medical team confirmed he has damaged the medial ligament in his knee.
The England international injured his knee playing for England Sevens at the World Cup in Hong Kong 10 days ago and was ruled out of last Saturday's win over London Irish.
Paul is set to be out for between six and eight weeks and will be unavailable for Gloucester's final three Zurich Premiership games, and any play-off matches.
Commenting on www.gloucesterrugbyclub.com Melville said: "It's a set-back but in some ways sums up our season. We have just had so many people injured at crucial periods, but you only have to look around the Premiership to see that other clubs are in a similar situation."
Commenting on www.gloucesterrugbyclub.com Paul added: "It's a big disappointment. I'm concentrating on getting back to full fitness, and will be right behind the rest of the team as we push for the top three slot in the Premiership and next season's Heineken Cup."
Paul, who has missed only a handful of games in four seasons with Gloucester, will see a specialist next week who will assess whether an operation is required.
Despite the injury, Nigel Melville's fly-half options could be boosted for Gloucester's next Premiership game at home to Leeds Tykes on Saturday 9 April with the return of Duncan McRae.
The Aussie stand-off has had an injury hit season, with his most recent knee injury ruling him out since the defeat away at Quins at the beginning of February.
As well as McRae's possible return, 22 year-old Brad Davies, who played the full 80 minutes at number 10 for Gloucester in the 13-12 win over London Irish on Saturday, was in commanding form for Gloucester against the Exiles at the weekend.
Billy Twelvetrees spoke to Russ Hargreaves of Talking Rugby at England training ahead of Sunday's huge RBS Six Nations clash with Wales at Twickenham. The centre is relishing the challenge of fronting up against a smart and talented Welsh back line.
Tim Taylor spoke to Gloucester Rugby TV after the 31 year old fly half announced that he was retiring from professional rugby. The Derby-born pivot, is excited for what the future holds for his new business ventures despite his career being cut short by a knee injury.
Dan Robson spoke to Gloucester Rugby TV at Franklin's Gardens following the 39-13 loss to Saints. The scrum-half enjoyed his battle with Lee Dickson but was gutted at the result as the Cherry and Whites did not do themselves justice, falling off in the closing stages to the league leaders.
Speaking after the game at Franklin's Gardens, Director of Rugby Nigel Davies reflected on a disappointing final quarter which saw Northampton Saints ease their way to a comfortable 39-13 win on Saturday afternoon.
Gloucester Rugby TV caught up with Gareth Evans this week ahead of the trip to Northampton Saints in the Aviva Premiership. The back rower explained his pride in his performances this season but knows there is still a lot for him to learn.
Gloucester Rugby travel to take on the table topping Northampton Saints in the Aviva Premiership on Saturday. Director of Rugby Nigel Davies is well aware of the qualities of Jim Mallinder's side, but Gloucester are the only team to defeat the Saints in the league this season.
Gloucester number eight Ben Morgan is hoping to start against Wales a week on Sunday, a team containing a number of former club team mates. He told the RFU.com website that he's looking forward to the prospect.
Second row James Hudson spoke to the club website following the 25-20 victory over Harlequins about how missed chances made things nervy late on, on what was a hugely emotional day for the Gloucester team.
Dan Murphy spoke to Gloucester Rugby TV after the win over Harlequins. The front rower touched down for the crucial second half score and expressed his delight at the performance and insisted the importance to push on from it.
There will be a trio of Gloucester Rugby players in the England Rugby starting line up for Sunday's huge clash with Wales at Twickenham. Number eight Ben Morgan is named to start with Billy Twelvetrees and Jonny May continuing in the back line.
England Under 20s have named their side to take on Wales for Friday's Under 20 Six Nations clash at Kingston Park, and Gloucester Rugby duo Billy Burns and Ross Moriarty keep their places in the starting line-up, with Jonny Hill named on the bench.