The PNE manager is set to be missing three players from the engine room for the clash at the New York Stadium.
Ben Pearson and Alan Browne are serving bans, while John Welsh is unlikely to have recovered from a calf injury. Although the squad is well stocked with midfielders, it now looks a bit light in terms of tacklers.
Liam Grimshaw could come into the equation, even though his first appearance in midfield for North End at Newcastle last week did pass him by somewhat.
Grayson told the Evening Post: “It is five bookings for Ben Pearson so he is banned for Saturday.
“We will miss him but it is up to someone else to come into the team and help us along the way.
“I wouldn’t have thought that John Welsh will be fit for the game, so we will be without three midfield players, with Alan Browne also suspended.”
Browne serves the second game of a three-match ban following his red card early in the 6-0 defeat at Newcastle.
In the case of Welsh, he damaged a calf muscle against Brighton last month.
He is likely to return to action after the international break.
The options for the centre of midfield are Daniel Johnson, Paul Gallagher, Ben Pringle and Grimshaw.
Grayson admits Pearson’s absence is a blow, such has been the 21-year-old’s form in recent weeks.
“Ben has been outstanding for us,” said Grayson.
“It’s disappointing but in this day and age, bookings are given out quite cheaply.
“For Ben to have been out of the team and not even in the matchday squad at the start of the season, just shows what character he has to come back in and make an impact.
“I have always believed Ben is a very good player and now he is playing with a lot of confidence.
“He uses the ball well, gets around the pitch and likes to tackle too.
“Ben is a good midfielder who can do lots of jobs for us.”
Grayson’s selection options for the wing could be boosted this weekend by the return to action of Aiden McGeady.
The Republic of Ireland international resumed training last week after being sidelined since the start of October with a hamstring strain.
Said Grayson: “McGeady trained for most of last week but was not quite 100% ready for the Newcastle game.
“He will have the benefit of a full week’s training in the build-up to Rotherham and hopefully can be ready.
“With Jermaine Beckford and Marnick Vermijl getting back on the pitch as substitutes last weekend, we are getting more options available.
“Jermaine and Marnick both made an impact when they came on, which is what you want to see.
“We’ve had to be careful not to rush them back because of the nature of hamstring injuries.”