Both players featured for the Springboks against the All Blacks in an epic Test at Newlands last week, but are back in the blue and white hoops this week as Western Province look to secure a semi-final place.
Louw is at tighthead prop, alongside Bongi Mbonambi and JC Janse van Rensburg in the front row, while Leyds features on the wing, with Ruhan Nel moving to inside centre to partner Huw Jones in midfield.
The only other change to the starting line-up sees Jaco Coetzee on the flank for the coastal derby which kicks off at 15:00 at Kings Park on Saturday.
Western Province coach John Dobson said that his team will be going all out to secure a playoff place.
"We know that we need to raise our game as a team this weekend and the players will be going flat out to deliver the result,amp;" Dobson said.
"It will be a major challenge to go to Durban, but one that we have embraced as a team.amp;"
15 Damian Willemse, 14 Seabelo Senatla, 13 Huw Jones, 12 Ruhan Nel, 11 Dillyn Leyds, 10 Robert du Preez, 9 Dewaldt Duvenage, 8 Nizaam Carr, 7 Cobus Wiese, 6 Jaco Coetzee, 5 JD Schickerling, 4 Chris van Zyl (captain), 3 Wilco Louw, 2 Bongi Mbonambi, 1 JC Janse van Rensburg
Substitutes: 16 Ramone Samuels, 17 Caylib Oosthuizen, 18 Jan de Klerk, 19 Sikhumbuzo Notshe, 20 Justin Phillips, 21 Werner Kok, 22 EW Viljoen