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.
Willi Heinz scored Gloucester's second try as the Cherry and Whites overturned a disappointing first 40 minutes and 0-6 half time deficit, to earn a 26-18 Aviva Premiership victory over Bristol Rugby on Saturday.
It's the first Gloucester-Bristol derby at Kingsholm in over eight years this Saturday (kick off 4:30pm) and, previewing the game with the local media this week, Defence Coach Jonny Bell stressed that, with both teams in the bottom half of the table, they both need the points.
Speaking to the local media this week, Gloucester front rower John Afoa knows the challenge ahead this week against Bristol, and calls on the Cherry and Whites to make the most of home advantage as a determined squad look to bounce back from a narrow loss to Saracens.
Tom Savage speaks to GRTV and the local media as Gloucester went down by 24-20 at Saracens on Sunday afternoon. The second row was disappointed with the result, despite a strong showing from the hosts.
Speaking immediately after the game, skipper Willi Heinz thought that Gloucester had executed their game plan reasonably well and competed hard against Saracens. However, it wasn't enough but the squad will have plenty to work on this week ahead of the derby match against Bristol.
Gloucester may be coming off their best win of the season, the 38-16 victory over Wasps last weekend, but Director of Rugby David Humphreys admits that Sunday's trip to Saracens is an even tougher test.
Looking to try a new sport? Look no further than Walking Rugby as thanks to Gloucester Rugby you can come along and try out the fast-growing sport at taster sessions across the county, starting this Wednesday.
Gloucester return to European Rugby Challenge Cup action on Thursday evening with the visit of Stade Rochelais to Kingsholm (kick off 7:45pm). Early Bird ticket prices are available until 6:30pm on matchday.
Talk about a game of two halves. Things looked grim on Saturday as Gloucester trailed 0-6 to Bristol at half-time. However, Matt Scott's eighth try of the season got Gloucester off and running, and the visitors fell apart as the Cherry and Whites eased to a 26-18 bonus point Aviva Premiership win.