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 after the 40-29 Aviva A League win over Wasps Rugby, Academy Coach Rich Whiffin explained his pride in the squad to overcome a strong opponent and book their spot in next week's Aviva A League final.
Willi Heinz returned from injury to skipper Gloucester to a famous 16-14 win over Stade Rochelais on Saturday evening. Speaking after the game in France, Heinz admitted the win wasn't pretty but was full of courage and a great result for the club.
Billy Burns contributed all Gloucester's points in the 16-14 European Rugby Challenge Cup win in La Rochelle on Saturday evening, but dedicated the victory to the whole squad whilst also praising the travelling support.
Speaking after Gloucester's brave 16-14 win against Stade Rochelais which clinches a European Rugby Challenge Cup final spot, Director of Rugby David Humphreys paid tribute to the way the team had executed the game plan in a hostile environment against quality opposition.
Greig Laidlaw returns to the Gloucester Rugby squad this week, and his inclusion is an important one after a serious ankle injury. The Scottish scrum half is determined to drive the team forward in their European Rugby Challenge Cup semi final in La Rochelle this Saturday.
Gloucester take on La Rochelle in the European Rugby Challenge Cup semi-final in France on Saturday evening, with the Top 14 side the favourites in the eyes of the bookmakers. However, David Humphreys is looking for his side to rise to the occasion against a familiar opponent.
Speaking to GRTV after Saturday's 39-30 Aviva Premiership win over Sale, Mark Atkinson admitted that the performance wasn't perfect but that the team's character shone through in a game that could easily have slipped away.
Scotland scrum-half Greig Laidlaw is targeting a 'unique' finish to his Gloucester tenure in the European Rugby Challenge Cup final at the venue where his professional playing career began, BT Murrayfield Stadium (Friday 12 May).
Gloucester's young United side once again dug deep to take an illustrious scalp, overturning a half-time deficit to earn a 40-29 victory over Wasps and earn a place in the Aviva Premiership A League final.