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 in front of the iconic Clifton Suspension Bridge, Henry Trinder explained how important the West Country Challenge Cup is going to be for the Cherry and Whites in their preseason preparations.
Speaking to GRTV at preseason training this Tuesday, new signing Willi Heinz gave an update on his recovery from a leg injury and expressed his enjoyment since his arrival in new surroundings with Gloucester Rugby.
Speaking to GRTV after the 22-23 defeat against Bordeaux-Begles which denied Gloucester a place in next season's European Rugby Champions Cup, Nick Wood rued the momentary lapse in concentration which allowed the French side to snatch victory from the jaws of defeat.
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.
Gloucester Rugby and Scotland scrum half Greig Laidlaw is gearing up for Rugby World Cup with his international teammates, and speaking to the assembled media this week, Laidlaw is excited to be in familiar surroundings at the showcase tournament.
With 50 days to go until Rugby World Cup 2015 gets underway several of the nations that are set to take to the Kingsholm Stadium field during the pool stages were in action in Toronto in Round Three of the Pacific Nations Cup.