Lolesio was stretchered from the field after appearing to suffer whiplash in an ugly second-half collision in the Wallabies' 21-18 win over Fiji on Sunday.
While the playmaker has since been cleared of serious injury, the Wallabies are still waiting on a follow-up medical assessment to determine his availability for the Lions matches.
The youthful duo of Tom Lynagh and Ben Donaldson loom as quality replacements, but there was no denying who the Lions would least like to face on July 19.
"I think Lynagh has been excellent all year. I think Donaldson did really well when he came on. I think they're both quality players," said Lions assistant coach Sexton.
"But obviously Lolesio's their number one based on their last, whatever, 10 games. He played the majority of the big games under Joe (Schmidt), so he'll know Joe's way. So he'll be a loss for them.
"But as far as we know, it's a whiplash kind of precautionary thing, so we probably expect him to be back Saturday week."
The former Lions No.10 refused to bite when asked if he was surprised Wallabies coach Schmidt opted not to select veteran playmaker James O'Connor.
"I'm not going to question Joe Schmidt's selection, which is probably what you're hoping for, and create a headline," he said.
"But no, outstanding three guys that are in there. They're probably guys that know Joe's system, Joe's way of playing, and they're the three that Joe has gone with and the three we're preparing to play against."
Despite hopes of a fairytale international farewell, O'Connor also missed out on a berth with the AUNZ Invitational squad to take on the Lions this Saturday.
The visitors have not shied away from re-calling a veteran fly-half of their own in Owen Farrell.
In a bold move, Lions coach Andy Farrell drafted his 33-year-old son into the squad mid-way through the tour after Elliot Daly broke his arm against the Queensland Reds.
Despite not having played a game in 10 weeks since suffering a concussion playing for French side Racing 92 and not playing for England in almost two years, Sexton backed Farrell to make an immediate impact in his fourth Lions tour.
"As you'd expect with someone with that experience, he's fitted in. He must have had the playbook on the plane on the way over because he came in and he's not missed a beat," Sexton said.
"He's been on top of things in training and that's exactly why he picked someone with experience and knows about a Lions tour, because it might take someone else 10 days to fit in. He's hit the ground running."
Farrell was not named in the Lions squad to face the Brumbies on Wednesday but his dad confirmed he was in contention for the AUNZ XV clash on Saturday.
