Tom Curry, Josh Navidi and Adam Beard will make their British and Irish Lions debuts against the Sharks on Wednesday.
The Lions will be captained by Iain Henderson for the first time, as Conor Murray has been named among the replacements for the midweek game at Ellis Park.
England flanker Curry and Wales duo Navidi and Beard will refresh the pack along with Sam Simmonds, who is set to make his first international start for over three years.
Josh Adams will play no part after the wing scored four tries against the tourists' South African namesakes the Lions on Saturday, playing a starring role in a 56-14 rout.
Lions head coach Warren Gatland said: "Wednesday night is another chance for us to have a look at a few more combinations.
"I'm looking forward to seeing how the back row goes; it's an exciting mixture and one that we hope will offer something a bit different.
"We expect another physical test against a side who are known for their power play and ambition.
"My congratulations to Tom, Josh and Adam ahead of their first starts in a Lions jersey."
Lions team to face the Sharks:
Liam Williams, Anthony Watson, Elliot Daly, Bundee Aki, Duhan van der Merwe, Dan Biggar, Gareth Davies; Mako Vunipola, Luke Cowan-Dickie, Zander Fagerson, Iain Henderson, Adam Beard, Josh Navidi, Tom Curry, Sam Simmonds.
Replacements: Ken Owens, Rory Sutherland, Tadhg Furlong, Tadhg Beirne, Jack Conan, Conor Murray, Stuart Hogg, Chris Harris.