The South Africans have rested key players Jacques Kallis, Mark Boucher and Makhaya Ntini for the three one-dayers while including untried batsman Hamish Amla and spinner Paul Harris in the squad.
With the series also being the first for the Proteas since charismatic all-rounder Shaun Pollock quit international cricket last month, a lot of players are suddenly finding themselves under the spotlight.
"The absence of the proven performers offers a wonderful opportunity to the new players to stake their claim for spots in the team," South African skipper Graeme Smith said.
"Now that Shaun's gone, the all-rounder's spot is there for the taking as well. Our bowling attack is also young, it is all about how the players take up new challenges."
Bangladesh, still reeling from the 2-0 thumping in the preceding Test series, may not be the best test for their strength, but the visitors know that they cannot afford to treat them as pushovers.
They learnt this the hard way when Bangladesh upset them in a super eight clash in the World Cup last year, a defeat that still rankles the team which is currently just decimal points behind top-ranked Australia in one-day charts.
Bangladesh, who have won 36 of the 166 ODI matches since making their debut at the international stage in 1986, are grappling with problems of their own with injury and poor form dogging some of their key players.
Aftab Ahmed, a vital cog in the middle order, injured his cheekbone after a miscued pull off Jacques Kallis in the second Test and has been ruled out of the one-dayers.
They will also have a new wicketkeeper in Dhiman Ghosh who has impressed in local leagues but it remains to be seen if he can excel against a top international side.
With Habibul Bashar, their highest scorer in one-dayers with 2168 runs, also cooling his heels after a prolonged slump in form, the team looks short of experience.
The second and the third one-dayers will be played in Dhaka on Wednesday and Friday.
Bangladesh (from): Mohammad Ashraful (captain), Mashrafe Bin Mortaza, Tamim Iqbal, Junaid Siddique, Nazim Uddin, Shahriar Nafees, Shakib Al Hasan, Dhiman Ghosh, Abdur Razzak, Shahadat Hossain, Mosharraf Hossain Rubel, Syed Rasel, Farhad Reza, Roqibul Hassan.
South Africa (from): Graeme Smith (captain), Hashim Amla, Johan Botha, A.B. de Villiers, J.P. Duminy, Herschelle Gibbs, Paul Harris, Charl Langveldt, Albie Morkel, Morne Morkel, Andre Nel, Alviro Peterson, Dale Steyn.