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With just six rounds left of the Top 14 regular season, Perpignan face the threat of dropping into the relegation zone as they visit Clermont on Saturday.
The 2009 champions lie level with fellow giants Biarritz, just four points clear of the drop zone.
And they face a difficult to trip to Clermont, who are chasing a play-off semi-final spot and have been unbeaten at home for two season.
Wesley Fofana, Aurélien Rougerie and Julien Bonnaire have been given the weekend off by the Clermont staff, as has Perpignan prop Nicolas Mas.
Biarritz could well take a big step towards securing their own survival when they face bottom side Lyon, who are eight points adrift.
And with their internationals back in the mix, Biarritz will be looking to make it three wins in a row for the first time this season.
Bayonne, who occupy the other relegation spot, will also look to boost their survival hopes against 10th-placed Brive.
The Basques have not been playing badly but have just fallen short of a positive result on a number of occasions, notably away to Racing.
Brive have won three of their last five games and currently hold a seven-point gap on the relegation zone but with fixtures against Toulon, Racing, Toulouse and Clermont left to play this season, this will be one of their last chances to assure their survival.
Bayonne welcome Mike Phillips back from Six Nations duty and Cédric Heymans from injury but will be without centre Sam Gerber .
Fifth plays fourth as Castres entertain Montpellier with a home play-off the potential prize for the winners.
After a slow start to the season, Montpellier have lost just twice since late November to climb above their hosts this weekend.
Castres, on the other hand, have not won in three games but bounced back from a draw with Lyon to almost upset Toulouse a fortnight ago.
Third-placed Toulon host sixth-placed Racing Metro in another heavyweight clash.
Toulon - who will have to make do without suspended director of rugby Bernard Laporte in the changing rooms - are unbeaten since visiting Clermont on January 8 with three wins and two draws in their last five games.
Racing have also found some form as they get past their off-field issues and have won three on the trot against Lyon, Bayonne and Bordeaux.
Joe Van Niekerk will captain the home team, which includes Jonny Wilkinson and Matt Giteau but Benjamin Lapeyre and Alexis Palisson are doubtful starters.
Bolstered by the return of their internationals, Stade Francais will look to climb back into the play-off places with a win over Agen.
It promises to be a clash of different styles as Stade have scored 39 tries to Agen's 20 this season but the Parisians have conceded 43 compared to just 27 by Agen.
Agen still have an outside chance of making the play-offs but with fixtures against Montpellier and Toulon on the horizon, they will be happy to do enough to ensure they keep their place in the top flight.
Bad news for Stade is that South African lock Gerhard Mostert's season is over due to a shoulder injury.
The Top 14 action starts on Friday when Bordeaux host leaders Toulousehoping for a miracle to avoid being dragged into the scrap for survival below them.
A loss for the hosts will drop them right into the relegation mire and considering that Toulouse won their previous meeting by 50 points, Bordeaux face a tough task as they try to bring a four-game losing streak to an end.
Good news for Bordeaux is that South African scrum-half Heini Adams has passed a late fitness test.
Toulouse, though, have wasted no time in slotting a handful of their returning Six Nations players straight into the starting XV.
|Click here for more betting|
|Saturday 11th May|
|Castres 25 - 12 Montpellier|
|Friday 10th May|
|Toulouse 33 - 19 Racing Metro Paris|
|Stade Francais 19 - 16 Racing Metro Paris|
|Saturday 4th May|
|Biarritz 52 - 17 Stade Francais|
|Clermont Auvergne 67 - 3 Bordeaux-Begles|
|Montpellier 50 - 22 Perpignan|
|Racing Metro Paris 29 - 28 Castres|
|Mont de Marsan 33 - 36 Bayonne|
|Toulon 43 - 21 Agen|
|Toulouse 57 - 7 Grenoble|
|Saturday 20th April|
|Grenoble 25 - 24 Toulon|
|Agen 23 - 15 Perpignan|
|Bayonne 32 - 26 Montpellier|
|Bordeaux-Begles 16 - 0 Biarritz|
|Castres 44 - 17 Mont de Marsan|
|Clermont Auvergne 39 - 17 Toulouse|
|Sunday 14th April|
|Toulon 26 - 26 Clermont Auvergne|
|Perpignan 33 - 28 Biarritz|
|Saturday 13th April|
|Agen 20 - 28 Stade Francais|
|Bayonne 31 - 24 Grenoble|
|Montpellier 10 - 8 Toulouse|
|Friday 12th April|
|Castres 23 - 23 Bordeaux-Begles|
Read the thoughts and opinions of Stuart Barnes with skysports.com