Outhalf Finn Russell will miss Scotland's potentially decisive World Cup clash with South Africa after failing to shake off an ankle knock.
The influential playmaker has been key to Scotland’s opening two wins over Japan and the United States but remains on crutches after injuring his ankle in Sunday’s victory over the Eagles in Leeds.
Head coach Vern Cotter — who has announced 10 changes in his team to face the Springboks in Newcastle this Saturday — will now put his faith in Russell's Glasgow team-mate Duncan Weir as he seeks the win which could clinch the Dark Blues a quarter-final slot.
Scotland lead Pool B on 10 points, while two-time former winners South Africa are just three adrift in second, having picked up maximum points against Samoa and two bonus-points in their shock loss to Japan.
Scotland head coach Vern Cotter said: “This is a massive test for our team. Playing South Africa is one of the biggest challenges you can face as a rugby player.
“We’ll need to be very good on the day.”
For the second week running Cotter has announced sweeping changes to the starting line-up, leaving a number of his big hitters on the bench even though they could clinch qualification with a win.
New arrival Blair Cowan — left out of the original 31-man squad — goes straight into the side at seven just days after replacing injured lock Grant Gilchrist.
He takes the place of John Hardie, who continues the return-to-play protocol after the head knock he sustained in the opener against Japan.
Prop Gordon Reid and centre Richie Vernon both start their first match of the campaign in place Ryan Grant and Mark Bennett, while Edinburgh scrum-half Sam Hidalgo-Clyne could join them from the bench.
Three further changes have been made to the starting back division.
Captain Greig Laidlaw returns at scrum-half, where he will partner Weir.
Wing Tommy Seymour starts in place of Sean Maitland and joins Tim Visser and Stuart Hogg in the back-three — the latter the only player to start all three matches for Scotland thus far.
In the forwards hooker Fraser Brown gets the start that evaded him against USA, when a back-row injury forced a late rotation.
He is joined by try-scoring prop Willem Nel, who switches roles with Jon Welsh once again, while the rested Jonny Gray returns to start alongside brother Richie, in place of the injured Gilchrist.
The changes are completed by Josh Strauss, who moves to the blindside flank at the expense of Alasdair Strokosch to accommodate number eight David Denton.
Scotland: Stuart Hogg; Tommy Seymour, Richie Vernon, Matt Scott, Tim Visser; Duncan Weir, Greig Laidlaw (capt); Gordon Reid, Fraser Brown, Willem Nel, Richie Gray, Jonny Gray; Josh Strauss, Blair Cowan, David Denton.
Replacements: Ross Ford, Alasdair Dickinson, Jon Welsh, Tim Swinson, Ryan Wilson, Sam Hidalgo-Clyne, Peter Horne, Sean Lamont.
