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.
Matt Kvesic, skipper for the night at Newcastle, praised the young and reshuffled Gloucester side for their commitment at Kingston Park but regretted the fact that Gloucester couldn't capitalise on an ideal opening to the game.
Speaking with the local media before the Gloucester team set off on the long trip north to Newcastle, Director of Rugby David Humphreys discussed his team selection and stated that Friday night's meeting will be a challenging one.
Speaking to the local media on Thursday, Matt Kvesic was looking forward to the trip to Newcastle Falcons, and the captain is looking to lead from the front with plenty for the Cherry and Whites to work on.
Gloucester saw a 12-0 lead overturned by Harlequins on Friday night as the visitors ran out 22-15 winners. After the game, Director of Rugby David Humphreys spoke about missed opportunities on the night.
Elton John and his band will visit the home of Gloucester Rugby, Kingsholm Stadium on Sunday 7 June as part of their European tour. This will be Elton's first ever performance in Gloucester and tickets are on general sale from 9am on Friday.
Mitcheldean finance specialist Simplicity is proud to become the latest sponsor of Gloucester Rugby. Keen-eyed supporters will notice Simplicity's PayrollSimply logo on Gloucester's ball boy bibs, stadium billboards and programme adverts.