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 after the 37-8 European Rugby Challenge Cup win over Benetton Treviso, James Hook admitted that the Italian side made things tough for Gloucester at times but that the Cherry and Whites are happy to take the bonus point win and turn their focus to Northampton next week.
Speaking to GRTV after the game, Backs Coach Tim Taylor was happy with the squad as they cruised to victory over Treviso. The result wasn't in doubt, but the Cherry and Whites laboured to secure a crucial try bonus point.
Speaking to the local media this week, Gloucester Rugby centre Matt Scott is excited to take the field again as the Cherry and Whites look to build on the win in Bayonne when Treviso come to Kingsholm this Saturday.
Defence Coach Jonny Bell admitted this week that the European Rugby Challenge Cup victory in Bayonne was a welcome one, stressed that Benetton Treviso will pose a tough test on Saturday at Kingsholm but that Gloucester are determined to deliver in front of their own fans.
Motu Matu'u is looking to make up for lost time this week as the Cherry and Whites head to Basque Country to take on Bayonne in the European Rugby Challenge Cup opener. The Samoan hooker made his first appearance in the jersey last weekend, and is hoping to contribute to the team this weekend.
Gloucester's attentions turn to Europe this weekend as they travel to Bayonne for their opening fixture of this season's European Rugby Challenge Cup. Forwards Coach Trevor Woodman told GRTV that the Cherry and Whites will be aiming to top their pool as they've done for the past two seasons, but is well aware of how tough it is to win in France.
Although understandably disappointed at seeing victory slip away at the last minute, Ben Morgan said after the game at Exeter that there were plenty of positives that Gloucester could take from the game.
Gloucester made it two wins from two outings in this season's European Rugby Challenge Cup as they outplayed Benetton Treviso at Kingsholm to win by 37 points to 8, the bonus point try coming with the final play of the game.