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.
Speaking to GRTV following the 16-9 victory over Exeter, Tom Savage felt that Gloucester needed that win after a tough few weeks and hopes that it acts as a springboard to a good end to the season for the Cherry and Whites.
A week on from '...letting down ourselves, the jersey and the supporters...', skipper Greig Laidlaw was full of praise for his team mates following the 16-9 Aviva Premiership win over Exeter Chiefs at Kingsholm on Friday evening.
With Gloucester looking to bounce back after exiting the European Rugby Challenge Cup last Saturday, Director of Rugby David Humphreys told the local media that the visit of Exeter Chiefs on Friday evening (kick off 7:45pm) will be a big test of character for the Cherry and Whites.
Rob Cook couldn't hide his disappointment when he spoke to GRTV following the 21-23 defeat at home to Newport Gwent Dragons on Saturday, stating that Gloucester simply hadn't been good enough on the day as their reign as European Rugby Challenge Cup holders comes to an end.
Speaking to the local media ahead of Saturday's European Rugby Challenge Cup quarter-final at home to Newport Gwent Dragons (kick off 12:45pm), Director of Rugby David Humphreys stressed that despite their difficult league campaign, the Welsh region will be a tough opponent at Kingsholm.
Saturday 30 April is the last day to join as a Club Member for the 2016-17 season and take advantage of your exclusive discount, for renewers, the discount is 15%, and if you wish, you can keep your seat.