Swans forward Michu has been sidelined until December, giving record signing Wilfried Bony a chance to shine, while the hosts are looking to escape the relegation zone.
The Spaniard, who picked up the injury in the Swans' 1-0 defeat against south Wales rivals Cardiff, is expected to return for the club's clash with Newcastle on Dec. 4.
In the meantime, record signing Wilfried Bony, who had reason to celebrate this week as the Ivory Coast booked its place at the World Cup, is likely to step in up front, having netted three goals in his last two outings for Swansea.
Fulham, meanwhile, will get a first taste of what it can expect from newly appointed head coach Rene Meulensteen. The short-lived Anzhi Makhachkala manager joined the west Londoners earlier this month, a move designed to ease the pressure on under-fire boss Martin Jol and cure the club's woes in front of goal.
The side has yet to net more than twice in a league match this season, while Dimitar Berbatov - who scored 15 times last year - has just one goal in 10 appearances this time around. Fulham has made a poor start to the Premier League season and sits 18th after just three wins in its first 11 matches, though it can leapfrog Swansea with a win.
New Fulham owner Shahid Khan is hoping the expertise of Meulensteen – a coach at Manchester United from 2001 to 2006 and Sir Alex Ferguson's assistant at Old Trafford from 2007 to 2013 – can help Jol as he seeks an upturn in fortunes.
Another priority for the Dutch duo will be improving Fulham's leaky defense as the Craven Cottage outfit has shipped 11 goals in its last three matches.
Defender Brede Hangeland is a doubt with a nerve problem in his leg, while Hugo Rodallega (groin), Sascha Riether (suspension) and Matthew Briggs (hernia) will certainly miss out for Fulham.
Combining domestic and continental commitments has proved a challenge this season for Swansea, which is 13th but just two points above the relegation zone. The club has not won in more than a month and will enter Saturday's fixture with just two triumphs since Sept. 22.
Swansea goalkeeper Michel Vorm will return from suspension but Michu (ankle), Pablo Hernandez (thigh) and Garry Monk (knee) are all still sidelined.