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.
Director of Rugby Nigel Davies was quickly able to identify a couple of key areas where Gloucester weren't quite good enough on the day, when he spoke to the media following defeat in The Stinger at Twickenham.
Huia Edmonds spoke to Gloucester Rugby TV this week ahead of Gloucester's clash with London Wasps in #TheStinger. The Australian hooker is yet to play at Twickenham and is excited at the prospect and putting things right on the pitch.
The bitter disappointment of losing against London Wasps in the Amlin Challenge Cup less than a fortnight ago, will give Gloucester ample motivation against the same opponent at Twickenham on Saturday says Director of Rugby Nigel Davies.
Billy Twelvetrees spoke to Gloucester Rugby TV following the 17-18 loss to Bath Rugby in Round Nineteen of Aviva Premiership Rugby. The Gloucester skipper said he was proud of the desire shown by his team at the end of a tough afternoon.
Nigel Davies spoke to Gloucester Rugby TV following the gutting 17-18 reverse to Bath on Saturday afternoon. The Director of Rugby expressed his pride at the efforts from his players and thanked the supporters for their incredible backing.
Nick Wood spoke to Gloucester Rugby TV this week ahead of Saturday's West Country derby clash with Bath Rugby. The front rower called on the squad to make a strong start and get the Kingsholm crowd behind them
Director of Rugby Nigel Davies admits that it's been a tough week at Gloucester Rugby following defeat at London Wasps last weekend, but that he's looking for his team to rise to the occasion for the huge game at home to Bath Rugby on Saturday.
Speaking immediately after the 36-24 Amlin Challenge Cup defeat at London Wasps on Sunday evening, skipper Billy Twelvetrees admitted that Gloucester left themselves with too much to do despite a spirited second half comeback.
Gloucester Rugby's trip to Twickenham ended in a 38-30 defeat to London Wasps in the sunshine. The hosts ran in 5 tries to Gloucester's three on a tough afternoon that despite plenty of promise saw Gloucester let down by errors.
England Under 18s have named their side to take on Ireland in the final of the FIRA/AER European Championship as they bid for a third consecutive title in Wronki, Poland, on Saturday, kick off 3.30pm BST.