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.
Gareth Evans was a first half replacement for the Cherry and Whites on Saturday afternoon, but the back rower's impressive carrying kept the hosts on the front foot when they needed it most to snatch a dramatic comeback win.
After his last ditch try clinched the 42-40 Aviva Premiership victory over Newcastle at Kingsholm on Saturday, Billy Burns told GRTV that all the Gloucester team deserve credit for hanging in there against a Falcons team who really made life tough for the Cherry and Whites.
Speaking ahead of Saturday's Aviva Premiership fixture at home to Newcastle Falcons (kick off 3pm), Director of Rugby David Humphreys emphasised the importance this weekend of Gloucester building on last week's impressive home victory against the Exeter Chiefs.
Speaking to the assembled national and local media, try-scorer Jonny May was delighted and relieved to have tasted victory on Saturday evening, and is looking forward to the European Rugby Challenge Cup final.
Tom Savage delivered a Man of the Match performance against Exeter Chiefs on his birthday on Saturday evening. He spoke to GRTV after the game about the importance of the European Rugby Challenge Cup win.
Speaking to the local media this week, John Afoa described the hard work that the Cherry and White have been putting in and that he is fighting fit ready for Saturday's European Rugby Challenge Cup semi final clash with Exeter Chiefs.
An independent disciplinary hearing today found that Mariano Galarza was selected for the Aviva Premiership match against Sale Sharks on March 29th, when he did not hold effective registration for Gloucester Rugby. The club was fined £5000 and received a two point deduction, suspended for two years.