The big game of the week sees second-placed Montpellier host mega-rich Toulon on Friday night.
Back-to-back thumping victories (36-6 and 54-15) over hapless Italians Zebre in the European Champions Cup, in which they ran in 13 tries, has lifted the struggling giants' spirits ahead of the return to domestic duty.
Currently sitting seventh and outside the end-of-season play-off places, Toulouse know a victory against Grenoble is crucial.
"We've got a positive dynamic. The players are starting to play well together and we hope to continue in that vein," said Toulouse's forwards coach William Servat.
But he knows Grenoble, who have by far the worst defence in the league, will be fired up having rested most of their first team in recent European Challenge Cup action, including last week's humiliating 71-3 defeat to Ospreys, just seven days after losing at home to the Welsh region 59-7.
"They chose to manage their squad. They want to survive in the Top 14 and we're expecting a physical battle," added Servat.
"They're short of confidence but when they find their game, they can be formidable."
The record four-time European and 19-time French champions have fallen on leaner times since their heyday of the 1990s and 2000s.
They last won the European title in 2010 and have not lifted the Top 14 crown since 2012. Last year they were battling just to finish in the top six and reach the play-offs.
The big game of the week sees second-placed Montpellier host mega-rich Toulon on Friday night in an encounter rendered all the more important by each side's European struggles.
Toulon's shock 22-21 reverse against Scarlets on Sunday means their knock-out stage hopes are hanging by a thread and the three-time champions will almost certainly have to win away to title-holders Saracens next month to stand any chance of progressing.
Montpellier likewise lost for a second time in four matches away to Castres 29-23 and face an uphill battle to get through a group in which three-time champions Leinster are flying.
Montpellier will have South African No. 8 Pierre Spies back but France international week Benjamin Fall is out with a leg injury.
Toulon sit fourth in a congested top half in which only five points separate Montpellier and eighth-placed Racing 92, the reigning champions.
Racing's recent league improvement -- they have lost only one of their last six -- is in stark contrast to their poor European form.
Three straight Pool 1 defeats means last season's finalists are already out of the Champions Cup.
Club president Jacky Lorenzetti called on his players to show humility to get their form back.
"We need to rediscover our mental strength," he said.
"We weren't humble (in the Champions Cup)... we're going to need to get undressed, take off our king's robes.
"We need to go down to the arena naked!"
Off the field they have more problems with South African utility back Johan Goosen retiring prematurely at just 24 years of age, ostensibly in order to release himself from his Racing contract.
Lorenzetti has threatened to sue Goosen, last season's Top 14 and Racing player of the year, for breach of contract while Toulon supremo Mourad Boudjellal called on all Top 14 presidents to show solidarity by refusing to sign the Springbok.
Elsewhere, leaders Clermont host 2015 champions Stade Francais while third placed surprise package La Rochelle are away to second form bottom Bayonne.
Fixtures (all times GMT):
Grenoble v Toulouse (1945)
Brive v Lyon (1600), Clermont v Stade Francais, Bordeaux-Begles v Pau, Bayonne v La Rochelle, Racing v Castres (all 1800), Montpellier v Toulon (2000)