Three teams - Sheffield Wednesday, Rotherham United and Derby County are aiming to finish 21st with two of the three sides set to be relegated to League One.
The Owls travel to the Rams while the Millers will make the trip to south Wales to take on Cardiff City. Both games kick off at 12.30pm.
Derby are the only team in control of their own destiny. Wayne Rooney's side are the current occupiers of 21st spot and if they beat Wednesday at Pride Park, they will retain their Championship status for another year.
The Owls and Rotherham must win their respective fixtures but then have to rely on other results to stay up. A draw for either of the Yorkshire outfits won't be good enough with Derby on 43 points, the Millers on 41 and Wednesday on 40.
Rotherham's superior goal difference means they will stay up if they defeat Cardiff and then Derby fail to beat Sheffield Wednesday.
A win for the Owls will see them move level on points with Derby and current goal difference means that a victory by any scoreline would be good enough for Darren Moore's side to go above the Rams.
They must then rely on Paul Warne's side failing to win at Cardiff City. Rotherham haven't won in seven games and have scored in just two of those outings.
Effectively, for Wednesday to survive - they need to win and Rotherham must fail to beat the Bluebirds. For the Millers, they need three points and then cross their fingers that the Owls get something from Pride Park.
With Sheffield United already relegated, an Owls relegation will mean both Steel City clubs have been demoted in the same season for the first time ever.
For Rotherham, it will make their last seven games feel like a huge missed opportunity.
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