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 Gloucester's final preseason friendly, a 29-24 defeat away at Scarlets, Director of Rugby David Humphreys reflected upon a performance that will form a crucial part of the Cherry and Whites preparations for the Aviva Premiership opener at Northampton next week.
Speaking to the media after the 45-8 preseason friendly victory over Munster, Director of Rugby David Humphreys wasn't getting too carried away, admitting that his team are making progress but that there's still a way to go.
Billy Twelvetrees spoke to Gloucester Rugby TV on Friday ahead of the pre season friendly with Munster Rugby. The club captain is excited to be back in the action at Kingsholm and experience the atmosphere again.
Gloucester Rugby Director of Rugby David Humphreys spoke to the local media after the 62-19 victory over Yorkshire Carnegie, and showed his delight at the first run out and stated there was still lots to work on ahead of the new season
Mark Atkinson made his first appearance in Cherry and White in the pre season victory over Yorkshire Carnegie on Saturday. Speaking to the local media, he was impressed with the first experience of Kingsholm.
Gloucester Rugby kick off their Aviva Premiership campaign at Northampton Saints on Friday evening, and then return home to entertain the same opponent in the A League at Kingsholm on Monday September 8th.
Gloucester Rugby travelled to West Wales for their third and final preseason game ahead of the start of the Aviva Premiership next week. The Scarlets were the opposition and Gloucester left Parc y Scarlets on the wrong end of a 29-24 scoreline.