Centre Frans Steyn surprised everyone in the South Africa camp on Tuesday when he withdrew for undisclosed reasons.
Coach Heyneke Meyer, who admitted earlier in the week that it had been arguably the toughest 10 days in the job, has also been beset by injuries, the latest being the withdrawal of Juan de Jongh.
"We don't really worry about it, we've kept our focus on the game," Matfield said in Umhlanga on Friday.
"A guy like Jan Serfontein is getting a chance and a few others have also come in.
"Whoever gets their chance, it's great for them. We're just looking ahead to the game."
Cheetahs wing Cornal Hendricks will make his debut for South Africa after playing in the unofficial "Test" against the World XV last week.
Meyer made three changes in total following that 47-13 victory in Cape Town, with prop Gurthrö Steenkamp, in his 50th test, scrumhalf Fourie du Preez and centre Jan Serfontein coming in.
They replaced Tendai Mtawarira and Ruan Pienaar, both on the bench, as well as Steyn.
Wales have never beaten the Springboks on South African soil and have only ever gotten the better of them once in 27 meetings.
"It's a proud record that we've got against them," Matfield, who will win a record-equalling 111th cap alongside John Smit, said.
"We would like to keep it that way."
The veteran lock warned, however, of two dangerous aspects of the Welsh game.
"Off defence they come hard off the line," he said. "That makes it difficult to attack against. We've worked on a few things to try and overcome that.
"Then they're also very good at phase play when the ball is in the right area of the field. We can't allow that and hopefully the guys that effect turnovers will have a good game."
Wales coach Warren Gatland, without several first-choice players through injury, named Gareth Davies and Matthew Morgan as the two uncapped players in his 23, both on the bench.
Adam Jones will win his 100th Test cap in the front row, while George North, named on the wing, faces a late fitness test after he missed training the bulk of the week through illness.
Despite stars like Sam Warburton and Leigh Halfpenny missing, New Zealander Gatland insists they can beat the Boks.
"We are not here to make up the numbers. We are here to build, get some confidence and hopefully to win the series."
Kick-off is at 17:05 on Saturday.
Teams:
Springboks:
15 Willie le Roux, 14 Cornal Hendricks, 13 JP Pietersen, 12 Jan Serfontein, 11 Bryan Habana, 10 Morné Steyn, 9 Fourie du Preez, 8 Duane Vermeulen, 7 Willem Alberts, 6 Francois Louw, 5 Victor Matfield (captain), 4 Bakkies Botha, 3 Jannie du Plessis, 2 Bismarck du Plessis, 1 Gurthrö Steenkamp
Substitutes: 16 Schalk Brits, 17 Tendai Mtawarira, 18 Coenie Oosthuizen, 19 Lood de Jager, 20 Schalk Burger, 21 Ruan Pienaar, 22 Johan Goosen, 23 Lwazi Mvovo
Wales:
15 Liam Williams, 14 Alex Cuthbert, 13 Jonathan Davies, 12 Jamie Roberts, 11 George North, 10 Dan Biggar, 9 Mike Phillips, 8 Taulupe Faletau, 7 Aaron Shingler, 6 Dan Lydiate, 5 Alun Wyn Jones (captain), 4 Luke Charteris, 3 Adam Jones, 2 Ken Owens, 1 Gethin Jenkins
Substitutes: 16 Matthew Rees, 17 Paul James, 18 Samson Lee, 19 Ian Evans, 20 Josh Turnbull, 21 Gareth Davies, 22 James Hook, 23 Matthew Morgan