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.
Previewing Friday evening's local derby at Bristol, Interim Head Coach Jonny Bell told the local media that Gloucester's preparations have gone well and that the whole squad is united in trying to finish the season on a high.
Speaking to GRTV this week, Acting Head Coach Jonny Bell spoke of his pleasure in the efforts and intensity in training from the squad after a tricky few weeks. The team were preparing for big games with Bristol and Cardiff in coming weeks.
Willi Heinz was understandably and visibly disappointed when he spoke to GRTV after the 27-30 home defeat to Harlequins, apologising to the home support as the game slipped away after seemingly having the game under control.
Speaking to the local media this week, Scottish centre Matt Scott spoke of the squad's determination to put in a big home performance against Harlequins, with vital points up for grabs in the hunt for a Top Six spot this Saturday (KO 3pm)
Looking ahead to Saturday's Aviva Premiership fixture at home to Harlequins (kick off 3pm), Head Coach Laurie Fisher told the local media that Gloucester will need to be on top of their game in a match which has big implications in terms of top six ambitions.
A big few days for the Gloucester-Hartpury Women side. First came the news that the team will compete in Women's Super Rugby next season, and on Saturday the team will play Worcester Ladies IIs at Kingsholm. Centre Hannah Jones and wing Michelle Ruddock spoke to GRTV this week to reflect on events.
Speaking to the local media after the 35-22 loss at Wasps, lock Tom Savage spoke of his disappointment at the result, with Gloucester left to rue a number of missed opportunities against a clinical home side.
Speaking after his return from England duty, Gloucester winger Jonny May reflected on England winning the Six Nations Championship, if not the Grand Slam, and what he needs to focus on to get back into the starting line-up.
Ross Moriarty started for Wales at the Stade de France on Saturday while Matt Scott was a replacement for Scotland. It was Scott who finished the day the happier, a try-scorer in a 29-0 victory over Italy.