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.
Gloucester Rugby will take on Wasps on Sunday in their first ever visit in the Aviva Premiership to the Ricoh Arena. Speaking to the local media today, Director of Rugby David Humphreys previewed the game as well as giving an update on the injured Henry Trinder.
Following the 48-10 Aviva Premiership win over London Welsh on Saturday, Dan Murphy praised his team mates for battling right up to the very last minute in difficult conditions and maintaining the momentum that the team have built in 2015.
Henry Purdy scored two memorable tries against London Welsh at Kingsholm on Saturday, and attributed the first one to hard work on the training ground before describing how much he's enjoying playing his rugby alongside friends like Callum Braley.
Gloucester face London Welsh for the third time this season when they meet at Kingsholm in the Aviva Premiership on Saturday (kick off 3pm), but Director of Rugby David Humphreys insists his team are prepared for a tough game against the Exiles.
Billy Burns was a late call up to the Gloucester team that lost narrowly to the Leicester Tigers at Welford Road on Friday evening and, speaking to GRTV post match, was full of praise for his team-mates but admitted that defeat was tough to take.
A number of the Gloucester Rugby squad this week benefitted from an initiative organised by Circle 2 Success (C2S) and the Rugby Players Association (RPA) to help players develop their business planning skills.