Popoali'i limped off the field in Sunday's opening ITM Cup game against Bay of Plenty with a hamstring injury.
It looked unlikely he would be available for the next couple of weeks and coach Tony Brown confirmed yesterday he was 50-50 at best for the shield challenge.
With Popoali'i (23) likely to be out of the loop, Otago will have a couple of greenhorns on the wing.
Kieran Moffat (24) made his debut for Otago on Sunday against Bay of Plenty while Fa'asiu Fuatai will take the place of Popoali'i on the left wing.
Fuatai (20) made his debut for Otago against Southland in a pre-season match earlier this month and has played just twice for Otago.
Popoali'i had a rough road injury-wise this year, out for nearly two months because of a foot injury.
Jayden Spence had an encouraging 20 minutes for Otago Country in the curtain-raiser to Sunday's game at Forsyth Barr Stadium.
Spence had always been scheduled to play just the 20 minutes as he continues his recovery from a head knock.
He suffered a bad concussion in late April and his 20 minutes on Sunday was his first rugby for nearly three months. He could play 60 minutes for the Otago development side or Otago Country this weekend.
Another Otago back option, Teihorangi Walden, played for Otago under-20 against the North Otago development team in Oamaru on Saturday as he also returns from a head knock. Prop Tama Tuirirangi is a 50-50 prospect as he recovers from a calf strain.
Otago will have just one training run today to recover quickly to be right for Friday night's match.