Polota-Nau fractured his forearm tackling Henry Speight just before half-time, while Smith hobbled off on the hour mark. Deans will name his preliminary 25-man squad for the Lions series on Sunday.
"Tatafu right from the outset didn't look good so he'll be devastated," Deans told Fox Sports after the match. "You don't get the sort of opportunity the Lions series presents very often and it looks like he'll be denied that now so that's very disappointing for him and for us."
The 110-cap veteran Smith, who played his last Test in 2010, had given his young Waratahs opposite number Michael Hooper a really tough test before he went off and it would have been interesting to see if he had done enough to be included in Deans' squad..
Smith is hoping to bridge the 12 year gap and join Brian O'Driscoll in returning from the 2001 series between Qantas Wallabies and the Lions. With David Pocock already ruled out, he could have offered invaluable experience to the squad.
"It could be significant but let's hope not because he's very keen to participate. We only resolved his elegibility yesterday and he didn't look great when he left but if he's talking positively, that's a good start," added Deans.
Brumbies coach Jake White later said doctors feared Smith had suffered a medial ligament injury, which would require surgery and rule him out of the Lions series.
Deans will add a further six players to his initial 25-man squad on June 11. The Lions open their 125th anniversary tour in Hong Kong on Saturday, 1 June against the Barbarians.