Whitelock has been diagnosed with a delayed-onset concussion and might also miss the third Test in Wellington on July 16 under World Rugby protocols which mandate a 12-day stand down for a player who sustains a concussion.
Vaa'i has also been ruled out of the Dunedin clash after testing positive for COVID-19.
"Again, not ideal," New Zealand captain Sam Cane said of the disruptions after training on Tuesday.
"Sammy was awesome at the weekend and became the second most capped All Black of all time, which is hugely impressive.
"We'll no doubt miss his leadership and what he brings, and then Tupou had been playing well all Super Rugby and was hanging out for his opportunity.
"So it's a tough pill for him to swallow but it's almost got to the stage where anyone who hasn't had it (COVID-19) ... it's lurking and it's going to strike soon and poor 'Tuups' had to get it this week."
New Zealand Rugby has approved a request from the All Blacks coaches to call up former Blues lock Patrick Tuipulotu who recently returned to New Zealand after a six-month sabbatical in Japan.
Tuipulotu has played 41 matches for the All Blacks without being able to establish himself as a first-choice selection.
The All Blacks also have the option of moving Scott Barrett from the blindside flank to the second row where he plays alongside Whitelock in Super Rugby Pacific for the Crusaders.
New Zealand won the first Test of the three-match series 42-19 at Auckland's Eden Park.
18°C