Melbourne have confirmed Harrison Petty's AFL debut and Irishman Darragh Joyce may do the same for St Kilda on Sunday at the MCG.
Three other players will play their first senior games this weekend, with Brayden Sier named for Collingwood in Saturday's away clash against Gold Coast.
Geelong have picked Quinton Narkle, and Brad Lynch will debut for the Western Bulldogs in Friday night's Etihad Stadium match.
It is also a big weekend for former Melbourne captain Jack Trengove, who plays his first game for Port Adelaide on Saturday when they take on Carlton at the MCG.
Petty is in his first year at Melbourne after they took him with the No.37 pick in last year's national draft.
His debut is part of Melbourne's process to work out how to cover for star recruit Jake Lever, who is out for the rest of the season with a knee reconstruction.
Lever and Demons assistant coach Matthew Egan, an All-Australian defender at Geelong, have been helping Petty prepare for senior football.
"We (he and Lever) have been going through game edits and watching him play, so I really want to play like him. He's been a really good one," Petty said.
"Matthew Egan ... he's really helped me with my fundamentals - my kicking, handballs and marking, so I really appreciate that."
Joyce has been in strong VFL form and he will be the 22nd Irishman to play in the AFL, if picked.
Essendon top-10 draft pick Aaron Francis will play his first senior game this season if he makes the final 22 for Sunday's big clash against North Melbourne.
North Melbourne are set to recall tagger Ben Jacobs from concussion.
Michael Walters will return from suspension to bolster Fremantle for their home clash on Sunday against Brisbane, who have lost Harris Andrews (concussion).
Sunday teams will be confirmed on Friday afternoon.