The men from Pretoria will be desperate to bounce back from last week's humiliating 35-7 defeat to Western Province, which marked their second Currie Cup loss in three outings.
With six Springboks backs from international duty, they will fancy their chances to pull this one off although coach Pine Pienaar needed no reminder of how big an advantage continuity in selection will be to the Lions.
“They grew as a side from the beginning and obviously with the Currie Cup if you can have most of your Super Rugby players, it will be beneficial for you,” said Pienaar
Springboks who were not available for the Bulls this week were centre Wynand Olivier, nursing a shoulder injury and wing Bjorn Basson recovering from concussion.
In the Lions squads, only flyhalf Elton Jantjies returned from the Bok-camp while fellow pivot Butch James and prop CJ van der Linde are still unavailable for this weekend.
Heading into the match, the Lions' coaching staff made the decision to leave out soon-to-be Bulls scrumhalf Jano Vermaak from the match 22, after he announced his decision to cross the Jukskei this week.
Michael Bondesio replaces Vermaak in an all-new halfback pairing with Jantjies and welcomed back from injury are wing Lionel Mapoe and fullback Jaco Taute.
Although this could be the Lions' best chance of knocking over their neighbours, forwards' coach Johan Ackermann warned of the dangers posed by a bruised Bulls team.
"The Bulls are a proud union and having those players back will definitely be a plus for them, but it will motivate us as well to put in a good performance” Ackermann said.
"We need to guard against those lapses where we lose concentration and, against the Bulls, you have to play 80 minutes – especially when their backs are against the wall.”
The last time these two sides met at Loftus, the Bulls scrapped out a 21-24 victory but on this occasion, the visiting side enter the match as favourites.
Ackermann, however, insisted his men will not be blinded by outside opinions.
"To be honest, we don't care about the other side, we want to focus on having a good campaign,” he said.
Kick-off is at 5.05pm.
Meanwhile, in an early match taking place in Bloemfontein, all eyes are on Springbok fetcher Heinrich Brussow expected to make his long-awaited return to the starting line-up against Western Province.
The Free State squad were further bolstered when regular skipper Adriaan Strauss, loosehead prop Coenie Oosthuizen and fierce loose forward Ashley Johnson were released by the national coach.
"With these players available, the Cheetahs' team have a Super Rugby look about them,” Province coach Allister Coetzee said.
Coetzee selected his same starting line-up which outclassed the Bulls last week with the added bonus of having flanker Pieter Louw on the bench.
Kick-off is at 3pm.