The forward pack has had a serious revamp and features a near-new front row, while two new loose forwards are starting.
Halfback Sean Romans gets his first start at this level since he faced the Waratahs in Sydney last February, coming in for captain Jimmy Cowan, who was forced home after dislocating a finger on his right hand in the 33-0 loss to the Stormers in Cape Town last weekend.
Outside Romans will be Mathew Berquist, who starts his first game since the first match of the season.
Berquist replaces Michael Hobbs, who, with loose forward Adam Thomson, has been dropped from the side after breaking of a team curfew in Cape Town.
Steven Setephano comes into the side to replace Thomson. With Nasi Manu not in South Africa because of injury, Setephano was coach Glenn Moore's only option at the back of the scrum.
Tim Boys gets his first start for the season in place of John Hardie, who moves to the bench.
Chris King gets a start in front of Clint Newland at tighthead prop, while beside him Jason Macdonald will get his first start in a Highlanders jersey since 2008.
Southland youngster Robbie Robinson moves on to the bench and should get some playing time.
After a week off because of the bye, the Bulls welcome back No 8 Pierre Spies, although lock Bakkies Botha is still missing, recovering from an Achilles injury.
But he should hardly be missed, as the experienced Danie Rossouw is set to start in the second row alongside captain Victor Matfield.
It is going to be an extremely demanding assignment for the Highlanders in Pretoria.
The Bulls have scored 17 tries in their three games.
The side has turned Loftus Versfeld into a imposing venue and the Highlanders, missing two of their key All Blacks and Hobbs, who has provided a spark this year, will be have to be on their game to have any hope of getting something out of the encounter.
• HIGHLANDERS v BULLS
Sunday, 4.05am, Pretoria
Highlanders: Israel Dagg, Ben Smith, Kendrick Lynn, Jason Shoemark, Fetu'u Vainikolo, Mathew Berquist, Sean Romans, Steven Setephano, Alando Soakai, Tim Boys, Tom Donnelly, Josh Bekhuis, Chris King, Jason Macdonald, Jamie Mackintosh (captain). Reserves: Jason Rutledge, Bronson Murray, Hayden Triggs, John Hardie, Scott Cowan, Robbie Robinson, James Paterson.
Bulls: Zane Kirchner, Gerhard van den Heever, Stephan Dippenaar, Wynand Olivier, Francois Hougaard, Morne Steyn, Fourie du Preez, Pierre Spies, Dewald Potgeiter, Derick Kuun, Victor Matfield (captain), Danie Rossouw, Werner Kruger, Gary Botha, Gurthro Steenkamp. Reserves: Bandise Maku, Rossouw de Klerk, Flip van der Merwe, Deon Stegmann, Jacques-Louis Potgieter, Jaco van der Westhuyzen, Pedrie Wannenburg.
