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.
Brighton is the venue of choice for England this week as the squad have reported for a training camp to prepare for the upcoming international against Wales. GRTV caught up with Gloucester's Matt Kvesic after the first day's training.
Speaking to GRTV after the game, Gloucester Rugby number eight Ben Morgan reflected on the loss to Northampton Saints, and spoke about what he and the team need to do for the new season when the team return after the summer break.
In only his second Aviva Premiership outing, Lloyd Evans scored his first senior try for Gloucester against Northampton Saints on Saturday and told GRTV afterwards that he enjoyed the experience despite finishing on the losing side.
Gloucester will round off their Aviva Premiership campaign on Saturday with a tough finale against Northampton Saints. Director of Rugby David Humphreys told the local media this week that he's pleased with the team's attitude over the past two games and is looking for more of the same.
Speaking to GRTV after the 12-11 Aviva Premiership victory at Sale Sharks on Friday evening, Matt Kvesic described it as a real team effort with several players having to play out of position due to illness and injury in the ranks.
Despite he and a number of his team mates playing out of position, Greig Laidlaw's four penalties were enough to help Gloucester to a 12-11 Aviva Premiership win at Sale on Friday evening. The skipper told GRTV after the game that everyone had played their part, especially the younger players.
Ross Moriarty played the full 80 minutes for Wales, while Matt Kvesic was a second half replacement for England as Eddie Jones' side defeated Warren Gatland's men by 27 points to 13 at Twickenham on Sunday.