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.
Dan Murphy was part of a Gloucester pack which took a grip as the Sale game progressed and, ultimately, were rewarded with a late penalty try. The loose head prop says the team's improved scrummaging is down to a lot of hard work over the summer.
Gloucester clinched their first Aviva Premiership win of the season on Saturday, 34-27 over Sale Sharks, and scrum half Greig Laidlaw felt that the Kingsholm crowd played a massive part as they spurred the team on.
David Humphreys spoke to Gloucester Rugby TV after the 34-27 win over Sale Sharks at Kingsholm. The Director of Rugby praised the Kingsholm crowd for spurring the team on to a super second half comeback.
Speaking to Gloucester Rugby TV this week, Sione Kalamafoni is expecting a tough, physical battle against Sale Sharks as the Cherry and Whites return to Kingsholm for Round Two of the Aviva Premiership
Previewing this weekend's Aviva Premiership fixture at home to Sale Sharks with the local media, Director of Media David Humphreys admitted he's looking forward to the team's first competitive outing in front of their own supporters.
Harlequins' intriguing trip to Kingsholm kicks off another bumper set of live Aviva Premiership Rugby matches on BT Sport. The 2012 Aviva Premiership Rugby Champions will now travel to face David Humphreys' Gloucester Rugby side on Friday 14 November for a 7.45pm kick-off.
Gloucester United got off to a flying start with an early try in this evening's Aviva Premiership A League fixture at Worcester Cavaliers, but it was downhill from there as the home side dominated in a 34-17 win.
Triumphant in their challenge, the Gloucester Rugby Former players have successfully completed the 969 mile journey from Land's End to John O'Groats despite the aches and pains they endured on the way.