De Villiers has sent a message to his players that the matches will act as trials for the squad which will defend its RWC title in 2011, saying he has "four chances to consider which players are good enough to represent South Africa at the World Cup".
In Wales he says he will consider "four or five" players plying their trade overseas, but whom he believes may still be able to add value to the Boks, meaning the Cardiff clash will launch many of the South African player's bids to attain their world cup dreams.
"We don't know how good the overseas players really are because the competitions there are different," said De Villiers. "Those four games are of critical interest on the road to the World Cup. By then we would have seen everyone in action."
And he hints that the Test against Wales will be a chance for many of his players to cement their places in his plans, as well as being one of few opportunities for his Northern Hemisphere based stars to impress.
"The best South African team will play against France after that (the Wales Test). We will (then) consider players in South Africa for the Tri-Nations unless we have a situation where the locally-based player is not as good as the one overseas."
Everyone in action will be over the course of the four match series will be contenders for the World Cup and, after France, De Villiers is planning on picking a team made up largely of South Africa's northern provinces for the Test against Italy in Witbank.
After that he will pick mostly from the provinces in the south for the second Test in East London, but he also suggests Wales may be his biggest test as a coach due to the preparation time available to him - comments that will be pleasing to Welsh ears.
"My ability as coach will be tested because I have a week to build a team," he said. "I know I may be shooting myself in the foot if my aim is to set records, but it's the right thing for South African rugby."
De Villiers hopes to take the 30 players he has identified for the World Cup squad on South Africa's potential Grand Slam tour at the end of the year.
"It will be the last opportunity to build a camp around rugby prior to the World Cup. If the players gel the way I think they can, we'll have cohesion the next time we tour.
South Africa will enter the Tri-Nations (against Australia and New Zealand) with their "best representative team
He will first consider players in South Africa, but he admits overseas-based players will be picked if they are better.
Finally, De Villiers also rubbished suggestions that the Azzurri will be taken lightly.
"We are not underestimating Italy at all. We have a lot of respect for them and consider them the best scrumming side in the world. They will test us thoroughly in the scrums and we'll get a good idea of who the best players are in that area," added De Villiers.
"I'm looking at a northern team in Witbank and a southern team in East London. It does not mean that we won't pick some guys from the south in the northern side and vice versa. We want to win those Tests.