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Both have already seen herculean service in a season of unique, extraordinary first-class length, and there is no let-up for either in starting terms as South Africa set their sights on avenging their 2010 defeat to Scotland at Murrayfield on Saturday (16:30 kick-off).
Following the announcement on Wednesday of the team to play the Scots – featuring the welcome inclusions of loosehead prop Gurthro Steenkamp and outside centre Juan de Jongh – it became clear that De Villiers and Du Plessis, the most prolific cap-holders in the backline and pack respectively for Edinburgh, are earmarked to close off the campaign having begun every Bok Test in 2012.
Certainly you would think that if these stalwarts, both of whom have been labouring to varying degrees with niggles and presumably also fatigue, have been entrusted with berths in the XV to play both Ireland and Scotland, they will also be expected to be at their posts for the customary tour climax against England next weekend.
If they do indeed “go the distance” they may well join Francois Hougaard as the only three players to have run out at the start of every match in the Heyneke Meyer tenure as coach thus far – although the versatile Hougaard has served both the scrumhalf and left wing positions and may well need a more convincing No 11 showing against the Scots if he is to retain a berth at Twickenham.
Earlier in the week, Meyer himself confessed he was “thinking of giving Jean a rest (at Murrayfield)” on the grounds of his continued battle to fully shrug off a hamstring complaint that has been bothersome for several weeks.
But considering the pressure on the coach to maintain a winning habit after the split-personality victory over Ireland, he instead opted to keep changes to a relative minimum and clearly wanted his regular skipper at the helm once more.
The decision to keep De Villiers in the mix would also have been influenced by the inclusion of De Jongh in place of Jaco Taute at No 13; it means the useful fielding of an all-Stormers midfield alliance and may only enhance the prospect of the potentially game-busting De Jongh shining.
Hopefully, the Boks will stamp their authority on the Scots in the first half, something they lamentably failed to do in Dublin, which could mean the luxury of hauling off De Villiers before the second half or early in it.
You can hardly blame Meyer -- yet to earn really significant public backing -- for seeking a strong sense of continuity after the ground-out triumph over a plucky but limited Irish outfit.
But it is also hard to imagine a team like the All Blacks, who have a better say over the game-time levels of their key assets anyway, flogging a player into the ground in the manner De Villiers has throughout the year – especially when he is clearly not wholly hunky-dory from a fitness point of view.
To compound matters, the blond No 12 also reportedly sat out Tuesday’s training because of a cold.
It is probably not unjustified to speculate that De Villiers and Du Plessis may be walking a bit of a tightrope in terms of trying to stay on the park for both Murrayfield and Twickenham: might the former game only damage their prospects of involvement in the possibly more crucial latter?
Just how close the Sharks tighthead prop is to more serious breakdown is reflected in the revelation that he hurt an ankle as early as the third minute against Ireland, yet soldiered on to the 55th before he finally became the first replacement of the day as Pat Cilliers mercifully took over his role.
Du Plessis has been a rock-like figure for the Springboks this year, and no doubt Meyer is fully aware of his contribution in a critical, anchoring position to the team’s overall good state of health in scrummaging terms.
The Scots do take pride in their own set-piece, so the Bok coach clearly believes that even a patched-up and increasingly tiring Du Plessis will be worth his weight in gold on Saturday.
The afore-mentioned trio of ever-presents for South Africa this season, plus Zane Kirchner (a contentious retention at fullback) will be the only starting survivors of the team which succumbed in torrential rain and biting cold 21-17 to the Scots two years ago.
Perhaps the most significant area of “all change” is in the back five of the pack: the starters at lock in the 2010 mudbath were Victor Matfield and Bakkies Botha, and the loose trio then was made up of Deon Stegmann, Juan Smith and Ryan Kankowski.
Long-range weather reports lean toward dry conditions this time, and with more than 50,000 tickets reportedly sold, the crowd will also be some 20,000 bigger than for the prior meeting when telly and fireside made infinitely greater sense to many of the local populace ...
*Follow our chief writer on Twitter: @RobHouwing
