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 the media following the 31-33 West Country Challenge Cup defeat to Exeter Chiefs at the Memorial Stadium, Director of Rugby David Humphreys was full of praise for his side's battling qualities in a bruising encounter but concerned about the injuries picked up.
The West Country Challenge Cup fixture against the Exeter Chiefs at the Memorial Stadium in Bristol on Saturday (kick off 3pm) will be Gloucester's last chance to work on things like new combinations says Director of Rugby, David Humphreys.
Speaking after the 30-21 West Country Challenge Cup defeat at Bath, Director of Rugby David Humphreys spoke of the improvements his team are making as preseason progresses but acknowledges that there is still work to do ahead of the start of the Aviva Premiership.
Speaking to the local media ahead of Saturday's trip to Bath Rugby in the West Country Challenge Cup, front rower Nick Wood spoke of the hard work put in across the extended preseason and highlighted the competition for front row spots in the squad.
Gloucester have named a 30 man squad for the latest round of West Country Challenge Cup action against Bath on Saturday, with Director of Rugby David Humphreys stressing the need to keep an eye on player workload ahead of what will be a long, tough season.
Describing the 50-7 West Country Challenge Cup win over Bath on Sunday as a '...good hit out...', wing Charlie Sharples admitted that it had been a good opportunity to put into practice things that the squad have been trying out in training in recent weeks.
Speaking to the local media after the 50-7 victory over Bath Rugby on Sunday, David Humphreys was happy with his squad's effort, with the most important aspect being the game time earned by his players.
Gloucester make wholesale changes to the side that started at Exeter last Saturday as they prepare to take on Bath at the Memorial Stadium, Bristol on Sunday in the West Country Challenge Cup (kick off 3pm). The Director of Rugby told GRTV that the players are raring to go and that he's looking forward to seeing different combinations in action.