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.
As Gloucester prepare for their 39th game of the season, against Bordeaux-Begles at Sixways on Sunday, David Humphreys told the local media that this week has been all about getting the players mentally and physically ready after a tough game against Connacht last Sunday.
Speaking to GRTV after the 40-32 victory over Connacht on Sunday, skipper Billy Twelvetrees explained that Gloucester had had to learn to be patient and cut out the errors to earn the win and progress to next weekend's final play-off against Bordeaux-Begles.
Jonny May's superb late score capped a thrilling 40-32 European play-off win over Connacht on Sunday. The winger spoke afterwards of his team's character and spirit as he looked ahead to one more week of rugby.
Speaking to GRTV this afternoon, Director of Rugby David Humphreys hailed the 'never say die' attitude of the team, after despite not being at their best, fighting back to take a 40-32 win after extra time over Connacht.
Jonny May continues on the wing on Sunday as Connacht come to town, and the England wing explains to the local media this week that he is delighted with his form and is looking forward to taking on Pat Lam's men.
Following the recent announcement that XBlades were to become the club's new kit and leisurewear partner, Gloucester Rugby can today (Tuesday 30 June) confirm the opening of a new retail unit, based at Gloucester Quays Outlet Centre, as well as the launch of a brand new online shop.