This clash between two of the traditional heavyweights of the South African game has plenty at stake, particularly for the Blue Bulls.
The spectre of possible relegation hangs over the Bulls, Western Province, Griquas and Free State Cheetahs but the nature of the tournament has been so that they are all still in the running for the two remaining semi-final places.
In contrast, the table-topping Sharks and Golden Lions are guaranteed of hosting home semi-finals in Durban and Johannesburg next weekend, but who their opponents will be is impossible to predict - as is the identity of the wooden-spoonists, who will have to fight for their Premier Division lives against the Eastern Province Kings in a promotion-relegation battle.
Lions caretaker coach Johan Ackermann knows matches against the Bulls are always physical and tense affairs and expects his side to be at their best win this clash.
With the Johannesburg-based side already assured of their place in the semi-finals, Ackermann has rested some of his first-choice players but he is adamant that his side will still be competitive.
"Regardless of what side we selected it would be a tough game because they (the Bulls) will be a full-strength side," he said.
"We are going out to win the game and there is no doubt in my mind that the players will feel the same.
"If the Bulls are good enough to beat us with the team they bring, then they deserve a place in the semis."
The Bulls are determined to win this clash after missing out on last year's semi-finals for the first time in a decade and there will be extra motivation after they lost 32-23 to the Lions at Loftus Versfeld in the corresponding match earlier this year.
Although they will be boosted by the return of several Springboks, the performance of fly-half Morne Steyn will be closely scrutinised.
Dropped for the final two Rugby Championship matches, he will be keen to prove to Bok coach Heyneke Meyer that he is not a spent force in the international arena.
Steyn's battle with Lions pivot Butch James will be one of the most important match-ups in this encounter.
Prediction: With the Lions not fielding their strongest XV and the Bulls' Boks back, there can be only one winner. Bulls to win by eight points which secures them the final play-off position.
Golden Lions: 15 Ruan Combrinck, 14 Deon Helberg, 13 Deon van Rensburg, 12 Alwyn Hollenbach, 11 Anthony Volmink, 10 Butch James (c), 9 Ross Cronje, 8 Willie Britz, 7 Derick Minnie, 6 Jaco Kriel, 5 Ruan Botha, 4 Michael Rhodes, 3 Pat Cilliers, 2 Callie Visagie, 1 CJ van der Linde.
Replacements: 16 Bandise Maku, 17 Jacobie Adriaanse, 18 Paul Willemse, 19 Warren Whiteley, 20 Whestley Moolman, 21 Elton Jantjies, 22 Lionel Mapoe.
Blue Bulls: 15 Zane Kirchner, 14 Akona Ndungane, 13 JJ Engelbrecht, 12 Francois Venter, 11 Bjorn Basson, 10 MornÃ¨ Steyn, 9 Jano Vermaak, 8 Arno Botha, 7 Jacques Potgieter, 6 Dewald Potgieter (c), 5 Flip van der Merwe, 4 JuandrÃ¨ Kruger, 3 Werner Kruger, 2 Willie Wepener, 1 MornÃ¨ Mellett.
Replacements: 16 Chiliboy Ralepelle, 17 Frik Kirsten, 18 Wilhelm Steenkamp, 19 CJ Stander, 20 Francois Hougaard, 21 Louis FouchÃ¨, 22 Dean Greyling.
Kick-off:19:10 local (18:10 BST, 17:10 GMT)
Referee: Craig Joubert
Rugby Union betting odds