Madine will be on the sidelines for up to six weeks after tests revealed he fractured a toe at Tranmere on Saturday while Buxton is out for a month after pulling a hamstring in training last week.
Gary Megson acted quickly to compensate for the loss of Madine by signing Arsenal youngster Sanchez Watt on loan. The 20-year-old, who can play wide midfield or as a central striker, was on loan with Leeds last season.
He joins Miguel Liera and James Tavernier as loan arrivals at S6 this week and, as with this pair, is available for the home game with Leyton Orient on Saturday.
Central defender Liera, 32, joins from Blackpool and has already played at Hillsborough this season, being a part of the Brentford team that took a point earlier this month while on loan with the Bees. Tavernier, 20, who can play at full back or in the middle of the defence, comes to S6 from Newcastle.
All three players are on loan until January and with skipper Rob Jones ruled out through suspension and Lewis Buxton sidelined, Megson could put Liera and Tavernier straight into the team to face Orient. Ryan Lowe is expected to continue up front in place of Madine, with Watt possibly on the bench.