Since winning the World Cup last October, the Springboks have enjoyed just a few weeks away from rugby and de Villiers says his players are now looking forward to a break.
"You look where we started last year in November; the players had three weeks off and then went straight into Super 14 and then it goes on and on and on," said de Villiers, who leads his side into the final match of their UK tour against England at Twickenham on Saturday.
"All of these guys played Currie Cup too. Fatigue is taking its toll.
"Physically they're trained to deal with it but there's a mental fatigue that nobody sees."
The Boks have already beaten Wales and Scotland on successive weekends and, even if both performances have been a little disappointing, de Villiers' men clearly have what it takes to produce winning rugby under difficult circumstances.
South Africa fly home after taking on England on Saturday, with de Villiers looking for one last big performance that will see them end the year on a real high and give the Lions a timely reminder of the size of the challenge ahead of them.
"They're thinking 'five days more and then I can go back to my family'. For the sake of the players, I'm so glad the year's done.
"Five days more and then it's the end of the year. It's going to be very difficult but I just hope they uplift themselves a little to the level we expect."