Both will be out for up to four weeks - lock Whitelock with a rib cartilage injury, and loose forward Messam with a thigh problem.
Their absence will place the microscope on the All Blacks' depth in their respective positions.
Locks Patrick Tuipulotu and Dominic Bird have been out with injury for some time but are on the verge of a return, and loose forward Jerome Kaino, whom Messam replaced a fortnight ago, remains a month away with an elbow problem.
However, coach Steve Hansen will take comfort from the way Jeremy Thrush played in the 28-9 victory over the Pumas at McLean Park.
Thrush was impressive during his 52 minutes on the field. He led the tackle count with 13, defended well and was solid in his core set-piece roles.
Sam Cane, who replaced Messam early in the second half, was another who shone. Both are candidates for starting roles against the South Africans at Westpac Stadium, although, rather than go for Cane, Hansen may opt for the extra grunt and lineout expertise Steven Luatua could provide at blindside flanker.
On reflecting on the work of his replacements, Hansen said: ''Sammy has worked very hard in previous seasons to show he's a true international.
''We've got a lot of faith in him. He's in our leaders' group and that's not often done when you're not in the starting XV. It shows how much respect we have for him.''
He said of Thrush, who was playing in his sixth test: ''He played really well and he can be proud of himself. Defensively he was massive. He got up and disrupted some of their lineout ball as well, scrummed well - he can be pleased.''
Thrush is likely to start alongside Brodie Retallick next Saturday, with Blues player Tuipulotu on track to return from an ankle injury to the reserves bench.
There was much to admire as the All Blacks kept up their perfect record against the Pumas. They played with ambition, despite the difficult conditions, and reaped the rewards. The scrum held up well - a tighthead after the halftime siren leading to a Messam try, and Aaron Smith scored his from a rock-solid shove on the Pumas' line.
Defensively, they were good. Israel Dagg returned with confidence, and Beauden Barrett played well in his first test start at first-five, goalkicking apart.
''I'm very pleased with the final result,'' Hansen said.
''We've played these guys three years in a row now, in not great conditions, and it's the first time we've got a bonus point, so very pleased to pick that up. [I'm] very pleased with the intent and the purpose of the side and how they came out.
''Yes, we made a few mistakes but we made them trying to do things and play positive rugby.''
Of the Springboks' challenge, Hansen said: ''There's been a lot of talk already from them about how they want and need to beat us because they haven't done so [in the Rugby Championship].
''We know what we're going to get and that's a fired-up side, so we need to prepare for that accordingly and be in the right frame of mind.''
By Patrick McKendry, of APNZ.
Rugby Championship
The scores
New Zealand 28
Julian Savea 2, Liam Messam, Aaron Smith tries; Colin Slade con, Beauden Barrett, Slade pen
Argentina 9
Nicolas Sanchez 3 pen
Halftime: 13-6
