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.
Tom Marshall scored his first Gloucester try in the 31-23 win over Saracens on Friday evening and was named Man of the Match. Talking to GRTV, he praised the forwards for setting the tone on the night.
Matt Scott was on media duty this week, and the Scottish international spoke about the benefit of having a full week of training with his club mates and the determination to get back to performing well against Saracens this Friday evening.
After the disappointment of last weekend's performance at Leicester, Director of Rugby David Humphreys told GRTV that he expects a big response from Gloucester in Friday's Aviva Premiership fixture at home to Saracens (kick off 7:45pm).
Gloucester travel to Tigers this Saturday in good spirits, and fly half Billy Burns is looking forward to testing himself in one of the toughest environments in the league as the Cherry and White hunt vital points as attention returns to the Aviva Premiership
After a good run of recent results, Gloucester will travel to take on Leicester in a good frame of mind according to Director of Rugby David Humphreys, but are well aware of the challenge that lies in wait.
Mental health and wellbeing is just as important as physical health, which is why the Gloucester Rugby Community team have partnered with Public Health Gloucestershire to become Mental Health First Aiders.
Gloucester Rugby continues to strengthen its commitment to working across Gloucestershire and the surrounding area and is looking to recruit an enthusiastic, motivated and dedicated individual to the role of Wheelchair Rugby Coach