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 15-3 Aviva Premiership defeat at Northampton, Director of Rugby David Humphreys couldn't criticise his team's effort in difficult conditions, but pinpointed the errors and indiscipline that allowed Stephen Myler to kick the home team to victory.
A handful of the Gloucester Rugby Mo-Bros visited Pride Hair Salon in Gloucester on Wednesday afternoon to have the final touches applied to their Movember efforts, and the team captain Jacob Rowan spoke to GRTV ahead of the final few days of the month.
Northampton away was the first Gloucester game under David Humphreys last season, but the Director of Rugby told the local media that the Cherry and Whites are a different proposition compared to 12 months ago and are looking forward to the challenge.
Having skippered Gloucester against the Barbarians last week, Nick Wood once again wore the captain's armband on Monday evening as Gloucester United kicked off their Aviva Premiership A League campaign with a bonus point win at Leicester.
Gloucester recorded a 32-20 win over La Rochelle on Thursday evening, and second row Jeremy Thrush was thrilled to pick up the victory on his first taste of a trip to France and the hostile atmosphere.
Gloucester were forced to battle for their 33-20 victory in La Rochelle on Thursday evening, something that centre Bill Meakes said that he and the squad were well prepared for as well as thanking the travelling support for the part they played.
Gloucester got off to a winning start in the European Rugby Challenge Cup last weekend, but Head Coach Laurie Fisher is expecting a much tougher challenge when the Cherry and Whites travel to La Rochelle for Thursday night's Round Two encounter.
After missing out on Gloucester's two recent European fixtures, Jonny May is back on the left wing for Friday evening's Aviva Premiership fixture at Northampton, while Mariano Galarza is named in the matchday squad for the first time this season.